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Inderbir Singh
G P Pal
HUMAN
EMBRYOLOGY
EIGHTH EDITION
INDERBIR SINGH
G.P. PAL
ft
© Inderbir Singh, 1976, 1979, 1981, 1985, 1986, 1996, 2001, 2007
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i Preface to the Eighth Edition
The eighth edition of HUMAN EMBRYOLOGY comes with several departures from earlier editions.
The book is now printed in a larger format. The drab black and white pages have given place to those
printed in full colour, and on much better paper. Paragraphs dealing with details that beginners can
skip are printed on a light blue background.
These cosmetic changes are accompanied by extensive revision of text to make it up to date. A new
chapter on 'Molecular Control of Development' has been added.
With printing in full colour, it has been possible to make a quantum jump in the quality of illustrations.
All illustrations are now in colour. Apart from addition of colour many old figures have been redrawn
and relabeled. Several new figures and tables have been added.
We are greatly indebted to Macmillan India Ltd. for their enthusiastic and wholehearted support
towards making this edition what it is.
We continue to be highly obliged to the numerous students and teachers who have written to us.
Their letters have been highly encouraging and useful.
This hook on human embryology has been written keeping in mind the requirements of undergraduate
medical students. The subject of embryology has traditionally been studied from imported textbooks
of anatomy or of embryology. Experience has shown that the treatment of the subject in most of these
books is way above the head of the average medical student in India. T h e difficulty has increased from
year to year as there has been, and continues to be, progressive deterioration in the standards of the
reaching of English in our schools and colleges. The combination of unfamiliar sophistications of
language and of an involved technical subject, has very often left the student bewildered.
In this book care has been taken to ensure that the text provides all the information necessary for an
intelligent understanding of the essential features of the development of various organs and tissues of
the human body. At the same time, several innovations have been used to make the subject easy to
understand.
Firstly, the language has been kept simple. Care has been taken not to compress too many facts into
an involved sentence. New words are clearly explained.
Secondly, simultaneous references to the development of more than one structure have been avoided
as far as possible. While this has necessitated some repetition, it is hoped that this has removed one of
rhe greatest factors leading to confusion in the study of this subject.
Thirdly, almost every step in development has been shown in a simple, easy to understand, illustration.
To avoid confusion, only structures relevant to the discussion are shown. As far as possible, the
drawings have been oriented as in adult anatomy to facilitate comprehension.
Fourthly, the chapters have been arranged so that all structures referred to at a particular stage
have already been adequately introduced.
In an effort of this kind it is inevitable that some errors of omission, and of commission, are liable
to creep in. To obviate as many of these as possible a number of eminent anatomists were requested to
read through the text. Their suggestions have greatly added to the accuracy and usefulness of this
book. Nevertheless, scope for further improvement remains, and the author would welcome suggestions
to this end both from teachers and from students.
6. The Placenta 59
Index 349
Chapter
moment of its inception up to the time when it is is referred to as the diploid (or double) number.
born as an infant. However, in spermatozoa and ova the number of
chromosomes is only half the diploid number, i.e.
twenty-three. This is called the haploid (or half)
Why a Medical Student should number. After fertilization the resulting zygote has
Study Embryology? twenty-three chromosomes from the sperm (or
1. This subject tells us h o w a single cell (the father), a n d t w e n t y - t h r e e from the o v u m (or
fertilized ovum) develops into a newborn, mother). The diploid number is thus restored.
containing numerous tissues and organs.
2. This knowledge helps us understand many
Autosomes and Sex Chromosomes
complicated facts of adult anatomy.
3. Embryology helps us understand why some The forty-six chromosomes in each cell can be
children are born with o r g a n s t h a t are divided into forty-four autosomes and two sex
abnormal. Appreciation of the factors res- chromosomes. T h e sex chromosomes may be of
ponsible for maldevelopment assists us in two kinds, X or Y. In a man there are forty-four
preventing, or treating such abnormalities. autosomes, one X-chromosome and one
Y-chromosome; while in a woman there are forty-
four autosomes and two X-chromosomes in each
Gonads and Gametes cell (Fig. 1.1). When we study the forty-four
The cells that carry out the special function of autosomes we find that they in fact consist of
reproduction are called gametes. The development twenty-two pairs, the two chromosomes forming
of a new individual begins when one male gamete a pair being exactly alike {homologous
{sperm or spermatozoon) meets and fuses with one chromosomes). In a w o m a n the two
female gamete (ovum or oocyte). The process of X-chromosutnes form another such pair; in a man
fusion of male a n d female g a m e t e s is called this pair is r e p r e s e n t e d by o n e X- a n d o n e
fertilization. The fused ovum and spermatozoon Y-chromosome. One chromosome of each pair is
form the zygote. The zygote later develops into derived from the mother and the other from the
an embryo and then into a fetus. father.
The male sex cells (spermatozoa) are produced
in the male gonads (testes) while the female sex Chromosome Structure
cells (ova) a r e p r o d u c e d in female g o n a d s
In a resting cell, chromosomes are not visible under
(ovaries). The formation of spermatozoa in the
a light microscope as their chromatin material is
testis is called spermatogenesis while the formation
highly dispersed. However, during cell division
of ova in the ovary is called oogenesis. The t w o
the chromatin network in the nucleus becomes
are collectively referred to as gametogenesis.
condensed into a number of chromosomes. The
To understand the structure of gametes and to
appearance of a typical chromosome is illustrated
study how they are formed, it is necessary to first
in Fig. 1.2. It is made up of t w o rod-shaped
review some facts regarding chromosomes and cell
structures or chromatids placed m o r e or less
division.
parallel to each other. The chromatids are united
to each other at a light staining area called the
SOME FACTS ABOUT CHROMOSOMES centromere (or kinetochore). Each chromatid has
two arms, one on either side of the centromere.
Haploid and Diploid Chromosomes Individual chromosomes differ from one another
The number of chromosomes in each cell is fixed in total length, in the relative length of the two
for a given species and in man it is forty-six. This arms and in various other characteristics; these
Some Preliminary Considerations
MAN
WOMAN
Significance of Chromosomes
Satellite.
The entire human body develops from the fertilized
11
Secondary
constriction"*" ovum. It is, therefore, obvious that the fertilized
Short arm ovum contains all the information necessary for
of chromatid formation of the numerous tissues and organs of
Centromere—* the body, and for their orderly assembly and
function. Each cell of the body inherits from the
\ fertilized ovum, all the directions that are necessary
Long arm \ for it to carry out its functions throughout life.
of chromatid '
This tremendous volume of information is stored
within the chromosomes of each cell.
LATE INTERPHASE
DNAof each
chromosome has under-
gone duplication.
and nucleoli d i s a p p e a r (Fig. 1.3D). W i t h the longitudinally into two so that the chromatids now
formation of the spindle, chromosomes move to a become independent chromosomes.
position midway between the two centrioles (i.e. At this stage the cell can be said to contain
at the equator of the cell) where each chromosome forty-six pairs of chromosomes. One chromosome
becomes attached to microtubules of the spindle of each such pair now moves along the spindle to
by its centromere. This stage is referred to as cither pole of the cell (Fig. 1.3F). This is followed
metaphase (Fig. 1.3E). In the anaphase the by telophase in which the two daughter nuclei are
c e n t r o m e r e of e a c h c h r o m o s o m e s p l i t s formed by appearance of nuclear m e m b r a n e s .
Human Embryology
MEIOSIS
2. Two homologous
As a l r e a d y s t a t e d m e i o s i s c o n s i s t s of t w o chromosomes come
successive divisions called the first and second to lie side by side
forming a bivalent.
meiotic divisions. During the interphase preceding
the first division, duplication of the D N A content
of chromosomes takes place as in mitosis. As a
result, another chromatid identical to the original
one is formed. Thus each chromosome is now made
up of two chromatids.
3. Four chromatids
First Meiotic Division are now distinct and
form a tetrad.
1. The prophase of the first meiotic division is
prolonged and is usually divided into a
number of stages as follows:
A NOTE ON CHRONOLOGY OF
EMBRYOLOGICAL EVENTS
HIGHLIGHTS
A spermatozoon has a head, a neck, a middle
piece and a principal piece or tail (Fig, 2.1).
Stages of spermatogenesis are summarized in
Fig. 2.5.
S p e r m a t o z o a are derived from r o u n d e d
spermatids. The process of conversion of a
s p e r m a t i d to a s p e r m a t o z o o n is called
spermiogenesis {Fig.2.6).
Stages of oogenesis are s u m m a r i z e d in
Fig. 2.8.
An ovarian follicle is a rounded structure that
contains a developing ovum surrounded by
follicular cells. The follicle has a fluid filled
cavity (Fig. 2.12).
O v a r i a n follicles have a cellular covering
called the theca interna. The cells of the theea In this chapter we shall first study the structure of
interna produce oestrogens (Fig. 2.13). a m a t u r e spermatozoon {male sex cell) before
considering its formation in the testis.
The follicle gradually increases in size and
finally bursts to expel the ovum. This process
of shedding of the ovum is called ovulation. STRUCTURE OF A MATURE
SPERMATOZOON
The corpus luteum is formed by enlargement
and transformation of follicular cells, after A spermatozoon is a highly specialized, free swim-
shedding of the ovum {Fig. 2.17), The corpus ming, actively motile cell. The spermatozoon has
luteum secretes progesterone, which is essential a head, a neck, a middle piece and a principal piece
for maintenance of pregnancy. or to'/(Fig. 2.1). An axial filament passes through
the middle piece and extends into the tail. The
spermatozoon measures about 60 um in length.
The Head
The head of the human spermatozoon is piriform
in shape and measures 4 urn in length. It is derived
Chapter
HIGHLIGHTS
A spermatozoon has a head, a neck, a middle
piece and a principal piece or tail (Fig. 2.1).
Stages of spermatogenesis are summarized in
Fig. 2.5.
S p e r m a t o z o a are derived from r o u n d e d
spermatids. The process of conversion of a
s p e r m a t i d to a s p e r m a t o z o o n is called
spermiogettesis (Fig.2.6).
Stages of oogenesis are s u m m a r i z e d in
Fig. 2.8.
An ovarian follicle is a rounded structure that
contains a developing ovum surrounded hy
follicular cells. The follicle has a fluid filled
cavity (Fig. 2.12).
O v a r i a n follicles have a cellular covering
called the theca interna. The cells of the theca In this chapter we shall first study the structure of
interna produce oestrogens (Fig. 2.13). a mature spermatozoon (male sex cell) before
considering its formation in the testis.
The follicle gradually increases in size and
finally bursts to expel the ovum. This process
of shedding of the ovum is called ovulation. STRUCTURE OF A MATURE
SPERMATOZOON
The corpus Iuteum is formed by enlargement
and transformation of follicular cells, after A spermatozoon is a highly specialized, free swim-
shedding of the ovum (Fig. 2.17). The corpus ming, actively motile cell. The spermatozoon has
Iuteum secretes progesterone, which is essential a bead, a neck, a middle piece and a principal piece
for maintenance of pregnancy. or tot/(Fig. 2.1}. An axial filament passes through
the middle piece and extends into the tail. The
spermatozoon measures about 60 urn in length.
The Head
The head of the human spermatozoon is piriform
in shape and measures 4 pm in length. It is derived
Spermatogenesis and Oogenesis
Fig. 2.3 Transverse section across the principal Fig. 2.4 Microscopic structure of a seminiferous tubule,
piece (tail) of a spermatozoon to show
the arrangement of fibrils. which fits into a depression (implantation
fossa) in the head.
s u r r o u n d e d by a spiral sheath m a d e u p of 3. In addition to the doublets, the axial filament
mitochondria. contains nine coarser petal-shaped fibrils, one
The axial filament is actually composed of such fibril lying just outside each doublet.
several fibrils arranged as illustrated in Fig. 2 . 3 .
There is a pair of central fibrils, surrounded by SPERMATOGENESIS
nine pairs (doublets) arranged in a circle around
the central pair. The whole system of fibrils is In a h u m a n m a l e , the f o r m a t i o n of g a m e t e s
k e p t in p o s i t i o n by a s e r i e s of c o v e r i n g s . ( s p e r m a t o z o a ) t a k e s p l a c e o n l y d u r i n g the
Immediately outside the fibrils there is a fibrous reproductive period, which begins at the age of
sheath. In the region of the middle piece the fibrous puberty (12 to 16 years) and continues even through
s h e a t h is s u r r o u n d e d by s p i r a l l y a r r a n g e d old age. Spermatozoa are formed in the walls of
mitochondria. Finally, the entire spermatozoon is the seminiferous tubules of the testes. If we look at
enclosed in a plasma membrane. one of these tubules under a microscope, we find
that there are many cells of different sizes and
Some Further Details shapes (Fig. 2.4). Most of these represent stages in
1. T h e c h r o m a t i n in t h e h e a d of t h e the formation of spermatozoa, but some (called
spermatozoon is extremely condensed. This Sertoli cells) have only a supporting function. The
makes the head highly resistant to various v a r i o u s cell-stages in s p e r m a t o g e n e s i s are as
physical stresses. T h e chemical basis for follows (the number of chromosomes at each stage
condensation is the replacement of histones is given in brackets) (Fig. 2.5).
by protamines.
2. The basal body is made up of nine segmented 1. The spermatogonia (type A) or germ cells
rod-like structures. O n its proximal side (i.e. (44 + X + Y) divide mitotically, to give rise
towards the head of the spermatozoon) the to more spermatogonia of type A, and also
basal body has a convex articular surface to spermatogonia of type B (Fig. 2.5).
Human Embryology
Spermiogenesis
T h e p r o c e s s by w h i c h a s p e r m a t i d
b e c o m e s a s p e r m a t o z o o n is c a l l e d
spermiogenesis (or spermateleosis)
(Figs 2.2 and 2.6). The spermatid is a
more or less circular cell containing a
nucleus, Golgi apparatus, centriole and
mitochondria. All these components take
part in forming the spermatozoon. The
nucleus forms the head. The Colgi
a p p a r a t u s is t r a n s f o r m e d i n t o t h e
acrosomic cap. The centriole divides into
two parts that are at first close together:
SPERMATIDS the axial filament appears to grow out
of them. O n e centriole becomes spherical
transformed and comes to lie in the neck. According
into to some w o r k e r s , the o t h e r centriole
forms the basal body, but according to
some others it forms the annulus. The
SPERMATOZOA part of the axial filament between the
neck a n d t h e a n n u l u s , b e c o m e s
Fig. 2.5 Stages in spermatogenesis. Note the number of s u r r o u n d e d by m i t o c h o n d r i a , a n d
chromosomes at each stage.
together with these forms the middle
2. The spermatogonia (type B) (44 + X + Y) piece. The remaining part of the axial filament
enlarge, or undergo mitosis, to form primary elongates to form the principal piece or tail. Most
spermatocytes. of the cytoplasm of the spermatid is shed, but the
3. The primary spermatocytes {44 + X + Y) now cell m e m b r a n e persists as a covering for the
divide so t h a t each of t h e m forms t w o spermatozoon.
secondary spermatocytes. This is the first The process of spermatogenesis, including
meiotic division: it reduces the number of spermiogenesis, requires about two months for its
chromosomes to half. completion.
Spermatogenesis and Oogenesis
Head
Cell
complex membrane
Axial filament -
Membrane covering sperm -
1 meiotic
division
^@
used throughout the fertile life of a woman are
produced at a very early stage (possibly before
birth) and do not multiply thereafter.
SECONDARY /
OOCYTE 1 22+X
k First
polar body Ova are derived from oogonia as shown in
Fig. 2.8. Note how similar the process is to
spermatogenesis. However, there are important
1
Second
meiotic
division ^2+Xj differences as well.
c)
Second
OVUM ( polar body Differences between
Spermatogenesis and Oogenesis
1. Observe that whereas one primary
Fig. 2.8 Stages in oogenesis (Compare each stage spermatocyte gives rise to four spermatozoa,
with the corresponding one in Fig. 2.5). one primary oocyte forms only one ovum.
Spermatogenesis and Oogenesis
2. When the primary spermatocyte divides, its • If fertilization does not occur, the secondary
cytoplasm is equally distributed between the oocyte fails to complete the second meiotic
two secondary spermatocytes formed. division, and degenerates in about 24 hours
However, when the primary oocyte divides, after ovulation.
almost all its cytoplasm goes to the daughter In each menstrual cycle, 5 to 30 primary
cell, which forms the secondary oocyte. The oocytes start maturing, but only one of them
other daughter cell (first polar body}, receives reaches maturity and is ovulated. The
half the chromosomes of the primary oocyte, remaining degenerate.
but almost no cytoplasm. The first polar body • During the entire reproductive life of a
is, therefore, formed merely to get rid of female only around 400 ova are discharged
unwanted chromosomes. (out of 40,000 primary oocytes available).
Further Details
Formation of Ovarian Follicles
• In the late fetal period primary oogonia
enlarge to form primary oocytes. We have seen that ova develop from oogonia
" At the time of birth all primary oocytes are present in the cortex of the ovary. The oogonia
in the prophase of the first meiotic division. are surrounded by other cells that form the stroma.
Their number is about 40,000. These stromal cells form ovarian or Graafian
The primary oocytes remain in prophase and follicles that surround ova and protect them. The
do not complete their first meiotic division stages in the formation of a follicle are as follows:
until they begin to mature and are ready to
ovulate. 1. Some cells of the stroma become flattened
• The reproductive period of a female is bet- and surround an oocyte (Fig. 2.9). These
ween 12 to 50 years of age. With each mens-
trual cycle, a few primary oocytes (about 5
to 30) begin to mature and complete the first
meiotic division shortly before ovulation.
• The first meiotic division of a primary oocyte
produces two unequal daughter cells. Each
Follicular cell
daughter cell has the haploid number of
chromosomes (23). The large cell, which Stroma
receives most of the cytoplasm, is called the
secondary oocyte, and the smaller cell is
known as the first polar body.
• The secondary oocyte immediately enters the
second meiotic cell division. Ovulation takes Zona pellucida
place while the oocyte is in metaphase. The
secondary oocyte remains arrested in
metaphase till fertilization occurs. Follicular cells
become columnar.
• The second meiotic division is completed
only if fertilization occurs. This division Basement membrane
results in two unequal daughter cells. The
smaller daughter cell is called the second
polar body. The first polar body may also Figs 2.9 and 2.10 Early stages in the formation of
divide during the second meiotic division. ovarian follicles.
Human Embryology
\ /
Microvillus
of oocyte
Zona peiiucida
Fig. 2.14 Diagrams to show the intimate relationship of oocyte and follicular cells. Gap junctions are
present between microvilli of the t w o .
Ruptured follicle
Stroma and theca
become very thin here. Ovum
microvilli of oocytes and of follicular cells. These compared to the thickness of the cortex of the ovary
junctions lie in the zona peiiucida (Fig. 2.14). (Fig. 2.15A). As it enlarges, it becomes so big that
Follicular cells are also responsible for it not only reaches the surface of the ovary, but
growth, metabolism and maturation of oocytes. also forms a bulging in this situation. Ultimately,
Conversely, oocytes are responsible for prolife- the follicle ruptures and the ovum is shed from the
ration and differentiation of follicular cells. ovary (Fig. 2.15D).
Factors produced in the oocyte help in formation Just before ovulation the follicle may have a
and maturation of Graafian follicles. diameter of 15 mm. The stroma and theca on this
side of the follicle become very thin. An avascular
area {stigma) appears over the most convex point
Ovulation
of the follicle. At the same time, the cells of the
The shedding of the ovum from the ovary is called cumulus oophoricus become loosened by
ovulation. The ovarian follicle is at first very small accumulation of intercellular fluid between them.
Human Embryology
Cells of
Spindle for second corona radiata
meiotic division Fate of the Ovum
Let us see what happens to the
ovum that is shed from the ovary.
You already k n o w that the ovary
is c l o s e l y e m b r a c e d by t h e
fimbriated end of the uterine tube.
T h e o v u m is, therefore, easily
carried into the tube, partly by
the follicular fluid discharged
Fig. 2.16 Structure of o v u m at the time of ovulation.
from the follicle and partly by the
activity of ciliated cells lining the
tube. T h e o v u m slowly travels
t h r o u g h the t u b e t o w a r d s the
uterus, taking three to four days
t o d o so. If sexual intercourse
takes place at about this time, the
s p e r m a t o z o a d e p o s i t e d in the
vagina swim into the uterus and
into the uterine tube. One of these
s p e r m a t o z o a m a y fertilize the
Granulosa cells in Wall of follicle collapses Cells hypertrophy o v u m . If t h i s h a p p e n s , t h e
wall of follicle and becomes folded to form corpus luteum fertilized ovum begins to develop
into an embrvo. It travels to the
Fig. 2.17 Stages in the formation of the corpus luteum.
Spermatogenesis and Oogenesis
- Lutein pigment
Considerably enlarged,
cells of corpus luteum
uterus and gets implanted in its wall. On the other supplied with blood vessels for this purpose.
h a n d , if the o v u m (secondary oocyte) is not T h e o v a r i a n follicle itself has no blood
fertilized it dies in 12 to 24 hours. It passes through vessels, bur the surrounding theca interna is
the uterus into the vagina and is discharged. full of them. When the corpus luteum is
forming, blood vessels form the theca interna
invade it and provide it with a rich supply
C o r p u s Luteum
of blood.
T h e corpus luteum is an important structure. Its
m a i n f u n c t i o n is t o s e c r e t e t h e hormone T h e s u b s e q u e n t fate of the c o r p u s luteum
progesterone, but it secretes some oestrogen also. depends on whether the ovum is fertilized or not.
The corpus luteum is derived from the ovarian
follicle, after the latter has ruptured to shed the (a) If the ovum is not fertilized, the corpus luteum
ovum, as follows (Fig. 2.17): persists for about 14 days. During this period
it secretes progesterone. It remains relatively
1. When the follicle ruptures, its wall collapses small and is called the corpus luteum of
and becomes folded. menstruation. At the end of its functional
2. At this stage, the follicular cells are small life, it degenerates a n d forms a mass of
and rounded (Fig. 2.18A). They now rapidly fibrous tissue called the corpus albicans ( =
enlarge. As they increase in size their walls white body) (Fig. 2.19).
press against those of neighbouring cells so (b) If the o v u m is fertilized a n d p r e g n a n c y
that the cells acquire a polyhedral shape results, the corpus luteum persists for three
(Fig. 2.18B). Their cytoplasm becomes filled to four months. This is larger than the corpus
with a yellow pigment called lutein. They luteum of menstruation, and is called the
are now called luteal cells. The presence of corpus luteum of pregnancy.
this yellow pigment gives the structure a
yellow colour and that is why it is called the The corpus luteum of pregnancy may occupy
corpus luteum (= yellow body). Some cells one-third to half the total volume of the ovary.
of t h e t h e c a i n t e r n a a l s o e n l a r g e a n d The progesterone secreted by it is essential for the
contribute to the corpus luteum. maintenance of pregnancy in the first few months.
3. We have seen that the corpus luteum secretes After the fourth m o n t h , the corpus luteum is no
progesterone. This secretion has to be poured longer needed, as the placenta begins to secrete
into the blood like secretions of endocrine progesterone. Degeneration of the corpus luteum
g l a n d s . All e n d o c r i n e g l a n d s are richly in the early months of pregnancy is prevented by
Human Embryology
Primordial follicles
Corpus luteum
degenerates and Interstitial gland
becomes a corpus degenerates and
albicans. becomes a corpus albicans.
human chorionic gonadotropin (hCG) secreted by these follicles do not persist into the next ovarian
the trophoblast cells of the developing embryo. cycle, but undergo degeneration. The ovum and
T h e series of c h a n g e s t h a t begin with the granulosa cells of each follicle disappear. The cells
formation of an ovarian follicle and end with the of the theca interna, however, proliferate to form
degeneration of the corpus luteum constitute what the interstitial glands, also called the corpora
is called an ovarian cycle. An ovarian cycle has atretica (singular = corpus atreticum). These glands
an average duration of 28 days, with ovulation are believed to secrete oestrogens. After a period
occurring at mid-cycle, i.e. on the 14th day. of activity, each gland becomes a mass of scar
tissue indistinguishable from the corpus albicans
formed from the corpus luteum.
Fate of Ovarian Follicles
We have seen t h a t in each o v a r i a n cycle o n e
Ovarian Cycle and Hormones
follicle reaches maturity, sheds an o v u m , and
becomes a c o r p u s luteum. At the same time, The changes taking place during the ovarian cycle
several other follicles also begin to develop, but are greatly influenced by certain hormones pro-
do not reach maturity (Fig. 2.19). It is interesting duced by the hypophysis cerebri (see Chapter 3).
to note that, contrary to what one might expect, The hormones produced by the theca interna and
Spermatogenesis and Oogenesis
There is very little cytoplasm. The oocyte contains a large (a) During the first meiotic division,
This gives it high motility. amount of cytoplasm. the two chromosomes of a pair,
Shape is adapted for motility. Shape adapted to provide ample instead of separating at anaphase,
storage of nutrition for the embryo may both go to the same pole.
formed after fertilization.
(This is called non-disjunction.)
Spermatozoa are ot two All ova have (22+X) chromosomes.
chromosomal types The resulting gamete then has 24
(22+X)and(22+Y). chromosomes instead of the
normal 23 (Fig. 2.21).
Fig. 2.20 Differences between male and female gametes At fertilization by this gamete, the
zygote will, therefore, have 47
by the corpus luteum in turn influence other parts chromosomes; there being three identical
of the female reproductive system (notably the chromosomes instead of one of the normal
uterus), resulting in a cycle of changes referred to pairs. This is called trisomy. Depending
as the uterine or menstrual cycle. upon the particular chromosomes involved,
various abnormalities are produced.
Reproductive Period Trisomy of chromosome 21 results in a
condition called mongolism or Down's
In an individual the formation of gametes takes syndrome. In this condition the child has a
place only during the reproductive period which broad face, obliquely placed palpebral
begins at the age of puberty (10 to 14 years). In fissures, epicanthus, a furrowed lower lip,
women it ends between the ages of 45 and 50 years, and broad hands with a single transverse
but in men it may continue till the age of 60 years crease. Usually the patients are mentally
or more. retarded, and have anomalies of the heart.
The presence of an extra X or Y
Viability of Gametes chromosome can give rise to various
An ovum usually degenerates 24 hours after syndromes associated with abnormal
ovulation. However, at the most it may survive genital development, mental retardation
for two days. Similarly, sperms usually degenerate and abnormal growth. Some of these are:
48 hours after ejaculation, but may survive up to XXX (abnormal female); XXY (Klinefelter's
four days in female genital tract. syndrome: abnormal male); XYY
(abnormal male). In Klinefelter's syndrome
the subject is a male (because of the
ABNORMALITIES IN FORMATION presence of a Y chromosome). However,
OF GAMETES the testes are poorly developed leading to
1. Abnormalities of Form sterility and gynecomastia.
Spermatozoa may be too large (giant) or too Patients with XXX chromosomes show
small (dwarf). The head, body or tail may be two masses of sex chromatin in their cells
duplicated. The ovum may have an unusually and are sometimes referred to as 'super
Human Embryology
FIRST
MEIOTIC
DIVISION
SECOND
MEIOTIC
DIVISION
GAMETES
FERTILIZATION
with normal
gametes
containing
23 chromosomes
ZYGOTE
Trisomy Monosomy
one gamete (as described above), the other represented by a single chromosome. This
gamete resulting from the division has only is called monosomy (Fig. 2.21).
22 chromosomes (instead of the normal 23); The best-known example of this is a
and at fertilization the zygote has only 45 female with only one X chromosome
chromosomes. Hence one pair is (Turner's syndrome). In this syndrome the
subject is always a female (because of and some of the genes are duplicated.
absence of a Y chromosome). There is The other chromosome will be shorter
agenesis of ovaries. Associated deformities than normal, some genes being
include mental retardation, skeletal missing.
abnormalities, and folds of skin on the sides (iv) A piece separating from a chromosome
of the neck (webbed neck). may get inverted before joining
Non-disjunction may also occur during the opposite chromosome (inversion).
second meiotic division as shown in Although the same genes are present,
Fig. 2.22. their sequence is disturbed.
(c) Such anomalies may affect more than one
(f) We have seen that during cell division the
pair of chromosomes. Alternatively, one
centromere splits longitudinally so that
pair may be represented by more than three each chromatid becomes a separate
chromosomes. When this happens with the chromosome. Sometimes the centromere
sex chromosomes, individuals with the splits transversely producing two dissimilar
constitution XXXY, XXXXY, XXYY, or chromosomes. One chromosome is made
XXXX may be produced. up of the short arms of both chromatids,
(d) Sometimes a gamete may have the diploid while the other is made up of the long arms.
number of chromosomes so that the zygote These are called isochromosomes.
will have 46 + 2*3 (i.e. 69) chromosomes.
Chromosomal errors of the type
This is called triploidy. Higher multiples
described above may also occur during
of 23 may also be seen. Such fetuses are segmentation of the ovum. This results in
generally born dead. a fetus having a mixture of cells with
(e) Abnormalities in the process of crossing normal and abnormal chromosomes. This
over can result in a number of chromosomal is called mosaicism. Such individuals may
abnormalities as follows: also show various abnormalities.
(i) Part of a chromosome may get attached
to a chromosome of a different pair 3, Gene Abnormalities (Gene Mutations)
(translocation). Genes are responsible for normal embryological
(ii) Part of a chromosome may be lost development. A change in the structure of a gene
(deletion). may occur at the time of gametogenesis. This
(iii) The two chromosomes of a pair may may give rise to birth defects. The change in the
break at unequal distances. When each structure or function of a gene is called gene
piece joins the opposite chromosome, mutation. At present many birth defects are
one chromosome is longer than normal known which are caused by gene mutations.
I3
Chapter
HIGHLIGHTS
• The term menstrual cycle is applied to cyclical
changes that occur in the endometrium every
month. The most obvious feature is a monthly
flow of blood (menstruation).
• T h e m e n s t r u a l cycle is divided into the
following phases: postmenstrual, proliferative,
secretory, menstrual (Fig. 3.3).
• The menstrual cycle is also divided into the
follicular phase (in which changes are produced
mainly by oestrogens) and the luteal phase (in
which effects of progesterone predominate).
Both phases are of roughly equal duration.
• The main changes in the endometrium are:
(a) increase in thickness, (b) growth of uterine
glands, (c) changes in epithelial cells lining
the glands and (d) increase in thickness and
fluid c o n t e n t of t h e e n d o m e t r i a l s t r o m a The period of a woman's life in which she can
(Figs 3.4, 3.5). bear children is called the reproductive period.
• Just before onset of menstruation the blood T h e m o s t o b v i o u s feature of this period is a
supply to superficial parts of the endometrium monthly flow of blood from the uterus that is
is cut off (Fig. 3.6). This part is shed off and referred to as menstruation (or menses). The onset
rhere is bleeding. of menstruation (menarche) takes place at about
• The menstrual cycle is influenced by oestrogens, 12 years of age. Menstruation ceases to occur at
by progesterone, by the follicle stimulating about 45 years of age, and this is referred to as
h o r m o n e ( F S H ) , a n d by the l u t e i n i z i n g menopause.
hormone (LH). T h e m o n t h l y m e n s t r u a t i o n is the external
manifestation of a series of cyclic changes taking
place in the uterus. These changes constitute the
menstrual cycle. Simultaneously, cyclic changes
also take place in the ovaries, and these constitute
the ovarian cycle. The most important event in
the ovarian cycle is ovulation (Chapter 2).
Human Embryology
bleeding bleeding
\
Days
r One Menstrual Cycle -
To understand the menstrual cycle it is (b) The stroma fills the interval between surface
necessary to know the structure of the uterus. The epithelium and myometrium. It contains
wall of the uterus is made up of three layers. numerous simple tubular glands (uterine
glands).
1. The outermost layer or perimetrium is made
(c) The arteries that supply the endometrium
up of peritoneum.
tend to run vertically towards the surface.
2. The main thickness of the wall is made up
Some of these run spirally and supply the
of smooth muscle. This is the myometrium.
whole thickness of the endometrium, while
3. The innermost layer (corresponding to
others that remain straight are confined to
mucous membrane) is called the endo-
metrium. It is this layer which undergoes the basal part.
changes during the menstrual cycle.
The constituents of the endometrium are as follows PHASES OF THE MENSTRUAL CYCLE
(tig- 3.2).
The menstrual cycle is usually divided into the
(a) The surface of the endometrium is covered following phases, on the basis of changes raking
by a lining epithelium. place in the uterine endometrium (Fig. 3.3):
Lining epithelium
Straight artery
5 -
Cycle beams ? ''^fl
;V8
s\V
here.
28^W
O
if)
<
Q_ 26 1
•?° / %U11
<
LU
Corpus luteum
^U Secretory I12
Proliferative n I
begins to 24 \ U 13
degenerate. Jr14 m
23 N ^
^ ^ 1 5 Ovulation
21^^C= — ^ 1 6
20 17
IT
is called the luteal phase. Just before the CM
o n s e t of t h e n e x t b l e e d i n g , t h e r e is
1
lowering of levels of both progesterone
and oestrogens, and it is believed that
this 'withdrawal' leads to the onset of
menstrual bleeding.
Fig. 3.4 Uterine glands at various phases of the
The division of the menstrual cycle menstrual cycle.
Human Embryology
% B ^
Postmenstrual Secretory
Fig. 3.5 Changes in the epithelium of uterine glands during a menstrual cycle.
The Menstrual Cycle
Lining epithelium
. These layers
are shed off.
Lining epithelium is
reformed by proliferation
of cells lining the basal
parts of the uterine glands.
in
Secretory Endometrium Endometrium
endometrium at end of during the post-
menstruation menstrual phase
providing a suitable environment for the fertilized The mechanism for onset of menstrual bleeding
ovum, when it reaches the uterus. In the absence is as follows. A few hours before the onset of
of pregnancy, however, these measures are menstrual bleeding the spiral arteries get
abortive: the superficial parts of the thickened constricted so that blood supply to superficial
endometrium (stratum compactum and stratum parts of the endometrium is cut off. This
spongiosum) are shed off (Fig. 3.6B), and this is ischaemia leads to degeneration of the
accompanied by menstrual bleeding. endometrium and also damages the walls of
Menstrual bleeding causes the endometrium to the blood vessels themselves. Subsequently
be shed off bit by bit, and the blood along with when the arteries relax and blood again flows
shreds of endometrium flows out through the into the endometrium, it leaks out through the
vagina. At the end of menstruation, the damaged blood vessels. This leaking blood is
endometrium that remains is only 0.5 mm thick. responsible for gradual shedding of
It consists of the stratum basale along with the endometrium.
basal portions of the uterine glands (Fig. 3.6B).
The epithelium of these glands rapidly proliferates
and reforms the epithelial lining (Fig. 3.6C). Time of Ovulation in
Relation to Menstruation
The endometrial changes associated with the
menstrual cycle are confined to the body of the In a 28-day menstrual cycle, ovulation takes place
uterus. The cervical mucosa is not affected. at about the middle of the cycle (Fig. 3.3). The
Human Embryology
period between ovulation and the next menstrual occur only if intercourse takes place during a
bleeding is constant at about 14 days, but the time period between four days before ovulation to
of ovulation does not have a constant relationship two days after ovulation. The remaining days
with the preceding menstruation. This is so because have been regarded as safe period as far as
the length of the menstrual cycle in women may prevention of pregnancy is concerned. This
vary from one m o n t h to another. Hence, it is forms the basis of the so-called rhythm-method
difficult to predict the date of the next ovulation of family planning.
from the date of menstruation unless the woman
has very regular menstrual periods. B. Where pregnancy is desired
There are many methods of finding out the Knowledge regarding the time of ovulation is
exact time of ovulation, but the one commonly also of importance in cases of sterility (difficulty
used is the temperature method. In this technique, in having children), where the couple can be
the woman's body temperature is recorded every advised to have intercourse during the days most
morning. When these temperatures are plotted on favourable for conception.
a g r a p h , we get a curve like t h a t s h o w n in
Fig. 3.7. The temperature is low during actual
Correlation between Ovarian and
menstruation. Subsequently it rises. At about the Uterine Cycles
middle of the cycle, there is a sudden fall in The ovarian and uterine cycles run parallel to
temperature followed by a rise. This rise is believed each other. Both are of 28 days duration. The
to indicate that ovulation has occurred. uterine cycle is dependent on the ovarian cycle.
The uterine endometrium shows cyclic changes,
CLINICAL CORRELATION which are dependent on the hormones secreted
by developing ovarian follicles a n d c o r p u s
Importance of Determining the Time of luteum of the ovary (Fig. 3.8).
Ovulation and 'Safe Period'
A. Where pregnancy is not desired HORMONAL CONTROL OF OVARIAN
AND UTERINE CYCLES
After ovulation, the ovum is viable {i.e..it can
be fertilized) for n o t m o r e t h a n t w o d a y s . These cycles are under the control of various hormones,
Spermatozoa introduced into the vagina die which can be briefly summarized here (Fig. 3.9).
within four days. Therefore, fertilization can The hypothalamus acts as a major centre for
The Menstrual Cycle
OVARIAN
CYCLE
Fig. 3.8 Diagram showing correlation between ovarian and uterine cycles.
HYPOTHALAMUS
produces releasing factors
f
ADENOHYPOPHYSfS
produces
FSH LH
1
Formation & maturation Ovulation Formation of
of ovarian follicles corpus luteum
OVARY
0es,r
°9en Progesterone
Produced produced
ENDOMETRIUM
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Concentration maximum
two days before ovulation
PROGESTERONE
Level increases to maximum in the
secretory phase under influence ot LH.
Fig. 3.10 Concentration of the hormones FSH, L H , estrogen and progesterone during a normal menstrual
cycle. O v u l a t i o n occurs because of a LH surge just before ovulation.
is started 5 days after onset of menstruation. because the progesterone in the pill prevents
They are taken continuously without any break the secretion of FSH and LH by the pituitary.
as long as contraception is desired. N o r m a l This interferes with the maturation of follicles
menstruation occurs during the 7 days in which and ovulation.
pills without hormones are being taken. If the Stoppage of pills reduces levels of these
pills are taken regularly there is a regular hormones in blood. It is this withdrawal that
menstrual cycle of 28 days duration. leads to menstrual bleeding. Contraceptive pills
Presence of progesterone in the preovulatory have almost 100 per cent success in suppressing
phase prevents occurrence of ovulation. This is maturation of follicles and ovulation.
Chapter
Ampulla (6 cm)
Uterine part (1 cm) Isthmus (3 cm)
Fertilization
takes place here
Fig. 4.1 Path taken by the sperm (pink), and ovum (blue), for fertilization.
Human Embryology
- Zona peilucida
. Spindle of second
meiotic division
• Secondary oocyte
Nucleus ot
Female pronucleus
mature ovum (From nucleus of ovum)
Vitelline membrane
Male pronucleus
(From head of sperm)
Spermatozoon
entering ovum
Fig. 4.2 Some stages in the maturation of the o v u m : (A) O v u m just before o v u l a t i o n ;
(B) O v u m at the t i m e of o v u l a t i o n ; (C) O v u m at the time of fertilization;
(D) O v u m just after fertilization.
membrane of the oocyte, and in the zona to formation of two cells, each having
peilucida, ensure that no other forty-six chromosomes (Fig. 4.3).
spermatozoon can enter the oocyte.
4. The zona peilucida is altered due ro release Male pronucleus
of l y s o s o m a l e n z y m e s by t h e p l a s m a
membrane of the oocyte. This process is
called the zona reaction.
5. As soon as a s p e r m a t o z o o n enters the Female pronucleus
ovum, the latter finishes its second meiotic
division and the second polar body is
formed.
6. Entry of the sperm leads to metabolic
Each chromosome
changes within the ovum that facilitate its duplicates itselt.
development into an embryo.
7. Each chromosome in the male and female
p r o n u c l e i is m a d e u p of o n l y o n e
Each daughter cell
c h r o m a t i d . Replication of D N A takes has 23 pairs of
place to form a second chromatid in each chromosomes - one of
each pair derived
c h r o m o s o m e . In the cell division t h a t from the spermatozoon
follows, each chromosome splits into two and the other from the ovum.
(as in mitosis). Meanwhile a spindle has
formed and one chromosome of each pair Fig. 4.3 Behaviour of chromosomes during
moves to each end of the spindle. This leads fertilization.
Formation of Germ Layers
8. From w h a t has been said above, it will be 22 + Y chromosomes. We speak of these as 'X-bear-
clear that as a result of fertilization ing", or 'Y-bearing', spermatozoa. An ovum can
be fertilized by cither type of spermatozoon. If the
fa) the diploid chromosome number (46)
sperm is X-bearing, the zygote has 44 + X + X
is restored; chromosomes and the offspring is a girl. If the
(b) determination of sex takes place; and sperm is Y-bearing the zygote has 44 + X + Y
(c) the fertilized ovum begins to divide chromosomes and the offspring is a boy.
into several cells (i.e. it undergoes
Thus the sex of a child is 'determined' at the
cleavage).
time of fertilization. It will now be clear that one
9. The important points to note at this stage chromosome of each of the 2 3 pairs is derived
are that from the mother and the other from the father.
produced by the implanting embryo. This blocks form the second germ layer, the ectoderm.
the recognition of the embryo as a tissue foreign The embryo is now in the form of a disc
to the mother. having two layers.
A space a p p e a r s between the ectoderm
FORMATION OF GERM LAYERS (below) and the trophoblast (above). This
is the amniotic cavity (Fig. 4.6C), filled by
As the blastocyst develops further, it gives rise not amniotic fluid or liquor amnii. The roof of
only to the tissues and organs of the embryo but this cavity is formed by amniogenic cells
also to a number of structures that support the derived from the trophoblast, while its floor
embryo and help it to acquire nutrition. At a very is formed by the ectoderm.
early stage in development, the embryo proper Flattened cells arising from the endoderm
acquires the form of a three-layered disc. This is (or, according to some, from trophoblast),
called the embryonic disc (also called embryonic spread and line the inside of the blastocystic
area, embryonic shield, or germ disc). cavity. (This lining of flattened cells is called
The three layers that constitute this embryonic Heuser's membrane.) In this way, a cavity,
disc are: lined on all sides by cells of endodermal
origin, is formed. This cavity is called the
1. Endoderm {endo = inside) primary yolk sac (Fig. 4.6D).
2. Ectoderm (ecto = outside) The cells of the trophoblast give origin to a
3. Mesoderm (meso = in the middle)
These are the three germ layers. All tissues Inner cell mass
1. S o m e cells of t h e i n n e r cell m a s s
differentiate (i.e. they become different
from others) into flattened cells, that
come to line its free surface (lower in
Fig. 4 . 6 A ) . T h e s e c o n s t i t u t e t h e
endoderm, which is thus the first germ
layer to be formed. Fig. 4.6 Differentiation of endoderm and ectoderm,
2. The remaining cells of the inner cell mass and the formation of the amniotic cavity and
become columnar (Fig. 4.6B). These cells the yolk sac.
Human Embryology
mass of cells called the extra-embryonic inside of the trophoblast, and the outside of
mesoderm (or primary mesoderm). These the amniotic cavity, is called the parietal
cells come to lie between the trophoblast or somatopleuric extra-embryonic
and the flattened endodermal cells lining mesoderm. (It is also referred to as the
the yolk sac, thus separating these from each chorionic plate.) The part lining the outside
other. These cells also separate the wall of of the yolk sac is called t h e visceral
the amniotic cavity from the trophoblast or splancbnopleuric extra-embryonic
(Fig.4.7A). mesodenn (Fig. 4.7B).
T h i s m e s o d e r m is c a l l e d ' e x t r a - From Fig. 4.7B it is clearly seen that the
e m b r y o n i c ' ' b e c a u s e it lies o u t s i d e the extra-embryonic coelom does not extend
embryonic disc. It does not give rise to any into t h a t p a r t of the e x t r a - e m b r y o n i c
tissues of the embryo itself. mesoderm which attaches the wall of the
Small cavities appear in the extra-embryonic a m n i o t i c cavity t o the t r o p h o b l a s t . T h e
mesoderm. Gradually these join together to developing embryo, along with the amniotic
form larger spaces and, ultimately, one large cavity and the yolk sac, is now suspended
cavity is formed. This cavity is called the in the e x t r a - e m b r y o n i c c o e l o m , and is
extra-embryonic coelom (Fig. 4.7B) (also attached to the wall of the blastocyst (i.e.
called the chorionic cavity). W i t h its trophoblast) only by this unsplit part of the
formation, the extra-embryonic mesoderm extra-embryonic mesoderm. This mesoderm
is split into two layers. The part lining the forms a structure called the connecting stalk.
Amniot c cavity
Future connecting
, stalk
Amniotic cavity
Embryonic disc ^- Amnion
^-Chorion
."<-i^m
\ \ Secondary
yolk sac
J. W— Trophoblast
~"~—"-1 -. v
Splanchnopleuric
and
Extra-embryonic Primary yolk sac
mesoderm Somatopleuric
extra-embryonic
"^-—__A--^ mesoderm
Extra-embryonic coelom B
Fig. 4.7 Formation of extra-embryonic mesoderm and extra-embryonic coelom. Note carefully, the
composition of the amnion, and of the chorion.
Formation of Germ Layers
Formation of Chorion and Amnion: At this the lining cells. These cells are no longer
stage, two very important membranes are flattened but become cubical (Fig. 4.7B).
formed. One is formed by the parietal extra- 9. At this stage, the embryo proper is a circular
embryonic mesoderm (on the inside] and the disc composed of two layers of cells: the
overlying trophoblast (on the outside); this upper layer (towards amniotic cavity) is the
is called the chorion (Fig. 4.7B). The other ectoderm, the cells of which are columnar,
is t h e amnion w h i c h is c o n s t i t u t e d by while the lower layer (towards yolk sac) is
amniogenic cells forming the wall of the the e n d o d e r m , made up of cubical cells.
amniotic cavity (excluding the ectodermal There is no indication yet of a head- or tail-
floor). These cells are derived from the end of the embryonic disc (Fig. 4.8).
trophoblast. We have already seen that the 10. However, we soon see that, at one circular
amnion is covered by the parietal extra- area near the margin of the disc, the cubical
e m b r y o n i c m e s o d e r m , and that the cells of the endoderm become columnar. This
connecting stalk is attached to it. area is called the prochordal plate. T h e
T h e c h o r i o n a n d a m n i o n play an a p p e a r a n c e of t h e p r o c h o r d a l p l a t e
important role in child birth (parturition) determines the central axis of the embryo
and we will refer to these again. (i.e. enables us to divide it into right and
With the appearance of the extra-embryonic left h a l v e s ) , a n d a l s o e n a b l e s us t o
mesoderm, and later of the extra-embryonic distinguish its future head and tail ends
coelom, the yolk sac becomes much smaller (Fig. 4.9).
than before and is now called the secondary I I. Soon after the formation of the prochordal
yolk sac. T h i s a l t e r a t i o n in size is plate some of the ectodermal cells lying
accompanied by a change in the nature of along the central axis, near the tail-end of
Endodermal
Embryonic cells here b e c o m e
disc s e e n in columnar.
surface view.
Centra! axis
is now a p p a r e n t .
Tail e n d
Columnar ectoderm
Head end
B
Cubical endoderm
P r o c h o r d a l plate
Fig. 4.8 Embryonic disc before appearance of a Fig. 4.9 Embryonic disc after establishment of a
central axis. (B) represents a section central axis. (B) represents a section
along the axis XY shown in (A). along the central axis.
Human Embryology
the disc, begin to proliferate, and form an plate, the ectoderm and endoderm remain
elevation t h a t bulges into the a m n i o t i c in c o n t a c t . In l a t e r d e v e l o p m e n t , t h e
cavity. This elevation is called the primitive ectoderm and endoderm mostly persist as a
streak (Figs 4.10A, B). The primitive streak lining epithelium. On the other hand, the
is at first a rounded or oval swelling, but bulk of the tissues of the body is formed
with elongation of the embryonic disc it predominantly from mesoderm. As there is
becomes a linear s t r u c t u r e lying in the no mesoderm in the prochordal plate, this
central axis of the disc. region remains relatively thin, and later
12. The cells that proliferate in the region of forms the bucco-pharyttgeal membrane.
the primitive streak pass sideways, pushing 14. The primitive streak gradually elongates,
t h e m s e l v e s b e t w e e n the e c t o d e r m a n d along the central axis of the embryonic disc.
endoderm (Fig. 4.111. These cells form the The disc also elongates and becomes pear-
intra-embryonic mesoderm (or secondary shaped {Fig. 4.12).
mesoderm) which is the third germ layer. 15. We have seen that when the embryonic disc
The process of formation of the primitive is first formed it is suspended {along with
streak, and of intra-embryonic mesoderm a m n i o t i c cavity a n d yolk sac) from the
by the streak, is referred to as gastrnlation. t r o p h o b l a s t by t h e c o n n e c t i n g s t a l k
13. T h e intra-embryonic mesoderm spreads (Figs 4 . 7 , 4 . 1 3 ) . To begin w i t h , t h e
throughout the disc except in the region of connecting stalk is very broad compared to
the prochordal plate. Note that the the size of the embryo. As the embryonic
mesoderm extends cranial to rhe prochordal disc enlarges in size, and also elongates,
plate, and here mesoderm from the two sides the connecting stalk becomes relatively
becomes c o n t i n u o u s across the midline small, and its attachment becomes confined
(Fig. 4.1 2). In rhe region of rhe prochordal to the region of the rail-end of the embryonic
— Prochordal piate
Primitive streak
(Ectodermal cells Mesodermal cells spread
proliferate here.) sidewards from
primitive streak.
Primitive streak
j
B
B
Fig. 4.10 Appearance of primitive streak. (B) is a Fig. 4.11 Formation of intra-embryonic meso-
section along axis XY shown in (A). derm. (B) is a section along axis KL in (A).
Formation of Germ Layers
^ Prochordal plate
/ I J \ , Developing notochord
Primitive streak —•—Jl 1 \ ^ - " ' \ Intra-embryonic
^~T> 1 *-\^ mesoderm
Fig. 4.12 Spread of intra-embryonic mesoderm. Note that the mesoderm comes to lie
between ectoderm and endoderm in all parts of the embryonic disc except at
(1) the prochordal plate, (2) the cloacal membrane, and (3) the region of the
notochord.
disc (Fig. 4 . 1 3 ) . Some i n t r a - e m b r y o n i c region of the primitive streak and form the
mesoderm arising from the primitive streak, mesoderm. Other cells push the hypoblast aside
passes backwards into the connecting stalk and form the endoderm; while those that remain
(Figs 4.12, 4.13). As it does so, it leaves an form the ectoderm. Thus, according to this view,
area caudal to the primitive streak, where all the three germ layers are derived from the
ectoderm and endoderm remain in contact epiblast. It will be o b v i o u s t h a t the main
(i.e. mesoderm does not separate them). This d i f f e r e n c e f r o m c l a s s i c a l d e s c r i p t i o n is
r e g i o n is, t h e r e f o r e , s i m i l a r t o t h e regarding the formation of endoderm.
prochordal plate, a n d forms the cloacal According t o some workers, the prochordal
membrane (Fig. 4.12). plate and the neural crest also form some intra-
embryonic mesoderm.
ALTERNATIVE VIEW O F
F O R M A T I O N O F G E R M LAYERS USE O F STEM CELLS IN T H E
T R E A T M E N T O F DISEASES
The preceding account of the formation of germ
layers conforms to classical descriptions. Some By now readers must have realized that the cells
authorities describe the process differently, the of i n n e r cell m a s s h a v e t h e p o t e n t i a l t o
main points of difference being as follows: differentiate into three different germ layers
T h e layer of c o l u m n a r cells (Fig. 4.7A> (ectoderm, endoderm and mesoderm). Since all
(described above as ectoderm) is defined as the the cells, tissues and organs of the body are
epiblast. The layer of cuboidal cells (described formed from these three layers, the cells of the
above as endoderm) is defined as the hypoblast. inner cell mass are called embryonic stem cells.
Some cells of the epiblast migrate to the T h e s e s t e m cells c a n be m a i n t a i n e d a n d
Human Embryology
Primitive streak
-Extra-embryonic mesoderm
- Extra-embryonic coelom
Extra-embryonic
coelom
Fig. 4.13 Diagram showing the attachment of the connecting stalk to the caudal end of the
embryonic disc. Note the cells of the intra-embryonic mesoderm passing into the
connecting stalk.
5 Further Development of
Embryonic Disc
B I^H
Notochordal process
Notochordal canal
process or bead process (Figs 5.1C, 5.2C, Some details of the process of formation of the
5.3A). The cells of this process undergo notochord are as follows:
several stages of rearrangement (Figs 5 . 1 ,
5.2) ending in the formation of a solid rod 1. After the formation of the blastopore, its
called the notochord. cavity extends into the n o t o c h o r d a l
p r o c e s s , a n d c o n v e r t s it i n t o a t u b e
As the embryo enlarges the notochord elongates called the notochordal canal (Figs 5.2D,
considerably and lies in the midline, in the position 5.3B).
to be later occupied by the vertebral column. 2. T h e cells f o r m i n g t h e floor of t h e
However, the notochord does not give rise to the notochordal canal become intercalated in
vertebral column. Most of it disappears, but parts (i.e. become mixed up with) the cells of
of it persist in the region of each intervertebral the e n d o d e r m (Fig. 5 . 3 C ) . T h e cells
disc as the nucleus pulposus. forming the floor of the notochordal canal
now separate the canal from the cavity of
the yolk sac.
3. The floor of the notochordal canal begins
to break d o w n . At first there are small
MMMMm (MfflSQMfflB openings formed in it, but gradually the
UZUJ-UJ* TXXXJJXD whole canal comes to communicate with
QDUJJJJ-XLU
the yolk sac (Fig. 5.3D). The notochordal
Notochordal process canal also communicates with the amniotic
Intra-embryonic cavity through the blastopore. Thus, at this
mesoderm stage, the amniotic cavity and the yolk
sac a r e in c o m m u n i c a t i o n with e a c h
other.
axtxamammw ffffflfflTffllfflffl-ffl 4. Gradually the walls of the canal become
flattened so that instead of a rounded canal
we have a flat plate of cells called the
Notochordal canal Notochordal plate
notochordal plate (Fig. 5.3E).
5. However, this process of flattening is soon
C F reversed and the notochordal plate again
becomes curved, to assume the shape of a
tube (Figs 5.3F, G). Proliferation of cells
of this tube converts it into a solid rod of
cells. This rod is the definitive (i.e. finally
G formed) notochord. It gets completely
separated from the endoderm.
1. The neural tube gives rise to the brain and The process of formation of the neural tube is
the spinal cord. referred to as neurulation.
2. The neural tube is formed from the ectoderm
overlying the notochord and, therefore, S U B D I V I S I O N S O F INTRA-
extends from the prochordal plate to the EMBRYONIC MESODERM
primitive knot (Fig. 5.4C).
3. The neural tube is soon divisible into: (a) a We have seen that the intra-embryonic mesoderm
cranial enlarged part that forms the brain, is formed by proliferation of cells in the primitive
Prochordal plate
Neural plate
Intermediate
mesoderm
Primitive streak
m m ly.v.
termediate mesoderm
Notochord mesoderm
Fig. 5.4 Subdivisions of intra-embryonic mesoderm. 'B' and 'D' are transverse sections across axes XY
(in A) and MN (in C) respectively. Note that the notochord and mesoderm are deep to the
ectoderm. Their position is shown diagrammatically.
Human Embryology
streak and that it separates the ectoderm and the coelom (Fig. 5.5C}. With the formation of the intra-
e n d o d e r m , e x c e p t in t h e following r e g i o n s : embryonic coelom, the lateral plate mesoderm
(a) prochordal plate fb) cloacal membrane, and splits into:
(c) in the midline caudal to the prochordal plate,
as this place is occupied by the notochord. 1. Somatopleuric or parietal, intra-embryonic
Cranial to the prochordal plate, the mesoderm mesoderm that is in contact with ectoderm.
of the two sides meets in the midline (Fig. 4.12). 2. Splanchnopleuric, or visceral, intra-
At the edges of the embryonic disc, the intra- embryonic mesoderm that is in contact with
e m b r y o n i c m e s o d e r m is c o n t i n u o u s with the endoderm (Figs 5.5B, D}.
extra-embryonic mesoderm (Fig. 5AD). The intra-
embryonic mesoderm now becomes subdivided T h e i n t r a - e m b r y o n i c c o e l o m gives rise t o
into three parts (Fig. 5.4): pericardial, pleural, and peritoneal cavities. Their
development will be considered later. For the time
(A) T h e m e s o d e r m , o n e i t h e r side of t h e being note that the pericardium is formed from
notochord, becomes thick and is called the that part of the intra-embryonic coelom that lies,
paraxial mesoderm. in the midline, cranial to the prochordal plate.
(B) M o r e laterally, the m e s o d e r m f o r m s a T h e heart is formed in the s p l a n c h n o p l e u r i c
t h i n n e r l a y e r c a l l e d t h e lateral plate mesoderm forming the floor of this part of the
mesoderm. coelom (Fig. 5.6). This is, therefore, called the
( Q Between these two, there is a longitudinal cardiogenic area (also called cardiogenic plate,
strip called the intermediate mesoderm. heart-forming plate). Cranial to the cardiogenic
The paraxial mesoderm now becomes area (i.e. at the cranial edge of the embryonic
segmented into cubical masses called somitomeres disc} the s o m a t o p l e u r i c and splanchnopleuric
which give rise to somites (also called metameres mesoderm are continuous with each other. The
or primitive segments) (Figs 5.4C, D). The first mesoderm here does not get split, as the intra-
somites are seen on either side of the midline, a embryonic coelom has not extended into it. This
little behind the prochordal plate. More somites unsplit mesoderm forms a structure called the
are formed caudally, on cither side of the deve- septum transversum (Fig. 5.6).
loping neural tube. The somites have an interesting
history which is considered in Chapter 7.
YOLK SAC AND
FOLDING OF EMBRYO
FORMATION OF THE
INTRA-EMBRYONIC COELOM The early history of the yolk sac has been traced
in Chapter 4 (Figs 4.6, 4.7}. We have seen that the
While the p a r a x i a l m e s o d e r m is u n d e r g o i n g primary yolk sac is bounded above by cubical
segmentation, to form the somites, changes are endoderm of the embryonic disc and elsewhere by
also occurring in the lateral plate mesoderm. Small flattened cells lining the inside of the blastocystic
cavities appear in it. These coalesce (come together} cavity. With the formation of the extra-embryonic
t o form o n e l a r g e cavity, c a l l e d the intra- mesoderm, and later the extra-embryonic coelom,
embryonic coelom. The cavity has the shape of a the yolk sac becomes much smaller; it comes to
horseshoe (Figs 5.5A, C). There are two halves of be lined all round by cubical cells; and it is then
the cavity (one on either side of the midline} which called the secondary yolk sac.
are joined together cranial to the prochordal plate. The changes that now take place will be best
At first, this is a closed cavity (Fig. 5.5A) but soon understood by a careful study of Fig. 5.7. N o t e
it comes to communicate with the extra-embryonic the following:
Further Development of Embryonic Disc
Intra-embryonic
mesoderm
Intra-embryonic coelom
opens into extra-embryonic
coelom here.
Amniotic cavity
Intra-embryonic
coelom
Extra-embryonic
coelom
Fig. 5.5 Intra-embryonic c o e l o m . (B) and (D) are sections across axes XY in (A) and (C) respectively.
(E) shows the relationship between the intra-embryonic and the extra-embryonic coeloms.
There is progressive increase in the size of and tail ends. These are called the head and
the embryonic disc. tail folds.
The head and tail ends of the disc (X, Y), With the formation of the head and tail folds,
however, remain relatively close together. parts of the yolk sac become enclosed within
H e n c e , the increased length of the disc the embryo. In this way, a tube lined by
causes it to bulge upwards into the amniotic endoderm is formed in the embryo. This is
cavity. the primitive gut, from which most of the
With further enlargement, the embryonic gastrointestinal tract is derived. At first, the
disc becomes folded on itself, at the head gut is in wide communication with the yolk
Human Embryology
Amniotic cavity
O *Q
Midgut
Foregut
Fig. 5.7 Formation of head and tail folds and establishment of the gut.
Further Development of Embryonic Disc
Embryonic Connecting
Extra-embryonic disc stalk
mesoderm
Amniotic
cavity
These are the lateral folds. As a result, the is a circular aperture which may n o w be
embryo comes to be enclosed all around by called the umbilical opening.
ectoderm except in the region through which 6. As the embryonic disc folds on itself, the
the vitello-intestinai duct passes. Here, there amniotic cavity expands greatly, and comes
Human Embryology
Amniotic /.
cavity / | Amniotic cavity
Extra-embryonic
coelom Mesoderm of ^_^_^m
A connecting stalk
1 B
Fig. 5.10 Allantoic diverticulum, and its relationship to the connecting stalk.
side of the hindgut into the connecting stalk the cavity (Fig. 5.13). The pericardium
(Fig. 5.10B). We will refer to it again while enlarges rapidly, and forms a conspicuous
considering the development of the urinary bulging on the ventral side of the embryo
bladder. (Fig. 5.14).
The septum transversum, which was the
EFFECT OF HEAD AND TAIL FOLDS most cranial structure in the embryonic disc
ON POSITIONS OF (Fig. 5.11), now lies caudal to the heart
OTHER STRUCTURES (Fig. 5.13). At a later stage in development,
the diaphragm and liver develop in relation
Just before the formation of the head and tail folds, to the septum transversum.
the structures in the embryonic disc are oriented,
as shown in Fig. 5.11. A median (midline) section Future Septum transversum
across the disc, at this stage, is shown in Fig. 5.12.
From the cranial to the caudal side, the structures Future Pericardial cavity
seen in the midline are (a) the septum transversum,
Prochordal plate
(b) the developing pericardial cavity and the heart,
(c) the prochordal plate, (d) the neural plate, Neural plate
(e) the primitive streak, and (f) the cloacal Position of
intra-embryonic
membrane. Note that the primitive streak is now coelom
inconspicuous. After folding, the relative positions
Somite
of these structures change to that shown in
Figs 5.13 and 5.14. The important points to note
here are as follows:
Developing spinal cord
1. With the formation of the head fold, the
developing pericardial cavity comes to lie Primitive streak
on the ventral side of the embryo, ventral Cloacal membrane
to the foregut. The heart, which was
developing in the splanchnopleuric
mesoderm in the floor of the pericardial Fig. 5.11 Embryonic disc showing the neural plate
cavity (Fig. 5.12), now lies in the roof of and related structures.
Human Embryology
Neural plate
Prochordal plate
Fig. 5.12 Embryonic disc and related structures just before the formation of the
head and tail folds.
Allantoic
diverticulum
Cloacal membrane
Fig. 5.13 Formation of head and tail folds. Also see Fig. 5.14.
Further Development of Embryonic Disc
Foregut
Cloacal membrane
Fig. 5.14 Later stage in the formation of the head and tail folds. Note the changing relationships of septum
transversum, pericardium, buccopharyngeal membrane, cloacal membrane and allantois.
3. The region of the prochordal plate now forms distal end of the hindgut is closed by the
the buccopharyngeal, or oral membrane, cloacal membrane. At first, this is directed
w h i c h c l o s e s t h e f o r e g u t c r a n i a 11 y. caudally (Fig. 5.13), but later it comes to
When this m e m b r a n e breaks d o w n , face ventrally (Fig. 5.14).
the foregut communicates with the
exterior. We have traced the development of the embryo
4. The most cranial structure of the embryo is to a stage when the rudiments of the nervous
now the enlarged cranial part of the neural system, the heart and the gut have been formed.
tube, which later forms the brain (Fig. 5.13). We are now in a position to trace the development
This enlarges enormously (Fig. 5.14). There of individual organ systems in detail. Before we
are n o w t w o big bulgings on the ventral do this, however, we must study the development
aspect of the embryo. Cranially, there is the of the placenta.
developing brain, and a little below it there
is the bulging pericardium (Fig. 5.14). In
Some Additional Points of Interest
between these t w o , there is a depression
called the stomatodaeum or stomodaeum, 1. In later life, r e m n a n t s of the primitive
t h e f l o o r of w h i c h is f o r m e d by t h e streak may give rise to peculiar tumours
buccopharyngeal membrane. that contain tissues derived from all three
5. Towards the tail end of the embryo, the germ layers. These t u m o u r s are seen in
primitive streak is n o w an inconspicuous the sacral region and are called
structure, that gradually disappears. The sacrococcygeal tumours.
Human Embryology
2. Experiments have shown that the of somites. In the head region, cranial to
formation of the neural tube is induced by somites, somitomeres give origin to some
the notochord. mesenchyme.
3. Somitomeres are not confined to the region 4. Wharton's jelly is rich in proteoglycans.
The Placenta
|6
which is a syncytium {cytoplasm with nuclei,
but no cell boundaries).
A developing e m b r y o gets attached to the
• The first-formed villi are called primary villi.
u t e r i n e e n d o m e t r i u m . T h i s is called
They consist of a central core of c y t o t r o -
implantation.
phoblast covered by syncytiotrophoblast.
In human beings the embryo gets buried in the
substance of the endometrium. This type of • Secondary villi have three layers. From inside
implantation is called interstitial implantation. o u t these are e x t r a - e m b r y o n i c m e s o d e r m ,
cytotrophoblast and syncytiotrophoblast.
After implantation the endometrium is called
the decidua. • In tertiary villi, blood capillaries are formed
in the extra-embryonic mesoderm.
The placenta is formed partly from embryonic
structures and partly from the decidua. It is • Villi are surrounded by an intervillous space
responsible for t r a n s p o r t of n u t r i e n t s and which contains maternal blood. As the placenta
enlarges, septa grow into the intervillous space
oxygen to the fetus, and for removal of waste
dividing the placenta into lobes. The fully
products.
formed placenta is about six inches in diameter
T h e essential elements of the placenta are and about 500 g in weight.
chorionic villi. The villi are surrounded by
maternal blood. Fetal blood circulates through • The placenta is normally attached to the upper
capillaries in villi. part of the body of the uterus. A placenta
attached lower down is called placenta praevia.
The maternal and fetal blood are separated by It can cause problems during child birth.
a very thin placental membrane (or barrier).
All substances passing from mother to fetus • The embryo is surrounded by three large cavities.
(and vice versa) traverse this membrane. These are the a m n i o t i c cavity, t h e e x t r a -
e m b r y o n i c coelom, and the uterine cavity.
The fetal tissue that takes part in forming the Enlargement of the amniotic cavity obliterates
placenta is chorion. It consists of trophoblast the extra-embryonic coelom, leading to fusion
(one layer of cells) resting on extra-embryonic of amnion and chorion. Further enlargement
mesoderm. of a m n i o t i c cavity o b l i t e r a t e s the uterine
Proliferation of cells of the trophoblast leads cavity. Fused a m n i o n a n d c h o r i o n (called
to formation of two layers: cytotrophoblast, membranes) bulge into the cervical canal
which is cellular and syncytiotrophoblast, (during child birth) and help to dilate it.
Human Embryology
IMPLANTATION
- Biasiocyst
Trophoblast
OffifflffiffifflHI^ $XU1T
Stroma
(Decidua)
DECIDUA
Decidua basalis
Amnion After the implantation of the embryo,
Choroin the uterine endometrium is called the
decidua. When the morula reaches the
uterus, the endometrium is in the
secretory phase. After implantation, the
features of the endometrium, which
are seen during the secretory phase of
the menstrual cycle, are maintained
Extra-embryonic and intensified. The stromal cells
coelom enlarge, become vacuolated, and store
Uterine lumen glycogen and lipids. This change in the
stromal cells is called the decidual
Myometrium
reaction.
Fig. 6.3 Manner of implantation in the human uterus. This The portion of the decidua where the
type of implantation is interstitial. Various other placenta is to be formed (i.e. deep to the
types occur in other mammals. developing blastocyst) is called the
decidua basalis (Fig. 6.4). The part of
The process of implantation is aided by proteo- the decidua that separates the embryo from the
lytic enzymes produced by the trophoblast. The uterine lumen is called the decidua capsularis,
uterine mucosa also aids the process. The while the part lining the rest of the uterine
trophoblastic cells which are situated over the cavity is called the decidua parietalis. The
inner cell mass, start penetrating the epithelium decidua basalis consists predominantly of large
of the endometrium. The implantation results decidual cells which contain large amounts of
due to the mutual interaction between tropho- lipids and glycogen (that presumably provide
blastic cells and endometrium. This interaction a source of nutrition for the embryo). The
is mediated by the receptors present on uterine decidua basalis is also referred to as the
epithelium and the secretion of 'L-selectin1 and decidual plate, and is firmly united to the
'integrins' by the trophoblast cells. chorion.
At the end of pregnancy, the decidua
Myometrium is shed off, along with the placenta and
membranes. It is this shedding off which
Decidua basalis
gives the decidua its name (c.f.
Chorion deciduous trees).
Decidua capsularis
FORMATION OF
CHORIONIC VILLI
Decidua parietalis
The essential functional elements of the
Uterine cavity
placenta are very small finger-like
processes or villi. These villi are
surrounded by maternal blood. In the
substance of the villi, there are
Fig. 6.4 Subdivisions or' decidua. capillaries through which the fetal blood
Human Embryology
1m
circulates. Exchanges between the maternal and
fetal circulations take place through the tissues
forming the walls of the villi (Fig. 6.5).
The villi are formed as offshoots from the surface
of the trophoblast. As the trophoblast, along with
.Capillary carrying the underlying extra-embryonic mesoderm,
fetal blood
constitutes the chorion, the villi, arising from it,
s Intervillous space are called chorionic villi.
containing
maternat blood The chorionic villi are first formed all over the
trophoblast and grow into the surrounding decidua
Blood vessels in
extra-embryonic
(Fig. 6.6A). Those villi related to the decidua
1 L^> mesoderm capsularis are transitory. After some time these
degenerate. This part of the chorion becomes
Fig. 6.5 Scheme to show that fetal b l o o d s m o o t h a n d is called t h e chorion laevae. In
circulating through capillaries of villi is i
contrast, the villi that grow into the decidua basalis
close relation to maternal b l o o d in the
intervillous space.
undergo considerable development. Along with the
tissues of the decidua basalis these villi form a
disc-shaped mass which is called the placenta
(Fig. 6.6B).The part ofthe chorion that helps form
Decidua basalis
the placenta is called the chorion frondosum.
T h e essential features of the f o r m a t i o n of
- Chorionic villi chorionic villi are as follows. The trophoblast is
at first m a d e u p of a single l a y e r of cells
(Fig. 6.7A). As these cells multiply, two distinct
layers are formed (Fig. 6.7B). The cells that are
nearest to the decidua (i.e. the most superficial
cells) lose t h e i r cell b o u n d a r i e s . T h u s , o n e
continuous sheet of cytoplasm containing many-
n u c l e i is f o r m e d . Such a t i s s u e is c a l l e d a
syncytium. Hence, this layer o f t h e trophoblast is
called the syncytiotrophoblast or plasmodio-
trophoblast. Deep to the syncytium, the cells of
the trophoblast retain their cell walls and form
the second layer called the cytotrophoblast (also
called Langhan's layer). The cytotrophoblast rests
on extra-embryonic mesoderm. All these elements
(syncytium, cytotrophoblast and mesoderm) take
Chorion laevae part in forming chorionic villi.
T h e following three stages in formation of
chorionic villi are seen:
Fig. 6.6 Two stages in the formation of chorionic (a) Primary villi consist of a central core of
v i l l i . Note their relationship to the c y t o t r o p h o b l a s t c o v e r e d by a layer of
decidua. In {B) note that the villi over the s y n c y t i o t r o p h o b l a s t . Adjoining villi are
decidua capsularis have disappeared. separated by an intervillous space.
The Placenta
4. Extra-embryonic meso-
A derm invades the centre of
each primary villus
(Fig. 6.12A). The villus
g r o o v e s . T h e n u m b e r of l o b e s
- Decidua generally varies between 15 and 20.
Each lobe c o n t a i n s a n u m b e r of
-Secondary villus
anchoring villi and their branches.
O n e such villus a n d its b r a n c h e s
- Syncytiotrophoblast
constitute a fetal cotyledon. The fully
- Cytotrop he-blast
formed placenta has 6 0 - 1 0 0 such
_ Extra-embryonic fetal cotyledons. The placenta n o w
mesoderm
forms a compact mass and is disc-
Maternal blood in shaped (Figs 6.17, 6.18).
intervillous space At full term (9 months after onset
of p r e g n a n c y ) the placenta has a
diameter of 6 to 8 inches and weighs
- Secondary villus
about 500 g. After the birth of the
- Syncytiotrophoblast child, the placenta is shed off along
with the decidua. The maternal
surface (formed by the decidual plate)
- Cytotrophoblast
is r o u g h a n d is s u b d i v i d e d i n t o
Extra-embryonic
mesoderm c o t y l e d o n s . T h e fetal s u r f a c e
(chorionic plate) is lined by amnion.
Fig. 6.12 Extra-embryonic mesoderm grows into the
It is smooth and is not divided into
cytotrophoblastic core of each primary villus,
cotyledons. The umbilical cord is
converting it into a secondary villus.
attached to this surface.
Decidua
Placental Membrane
Tertiary villus In the placenta, maternal blood circu-
lates through the intervillous space
Intervillous space
and fetal blood circulates through
Syncytiotrophoblast
blood vessels in the villi. The mater-
Cytotrophoblast
nal and fetal blood do not mix with
Capillary in extra-
each other. They are separated by a mem-
embryonic mesoderm
brane, made up of the layers of the
wall of the villus (Fig. 6.19A). These
Maternal blood in (from the fetal side) are as follows:
intervillous space
(a) the endothelium of fetal blood
v e s s e l s , a n d its b a s e m e n t
Tertiary villus membrane.
Syncytiotrophoblast
(b) surrounding mesoderm (con-
nective tissue).
(c) cytotrophoblast, a n d its base-
Cytotrophoblast
Capillaries in extra-embryonic ment membrane.
mesoderm (d) syncytiotrophoblast.
Fig. 6.13 Blood capillaries invade the extra-embryonic mesoderm of These structures c o n s t i t u t e the
each secondary villus thus converting it into a tertiary villus. placental membrane or barrier. All
The Placenta
I II II UE
m o s t villi, a n d by c o n s i -
Syncvtiotrophoblast d e r a b l e t h i n n i n g of t h e
Maternal blood in
connective tissue (Fig 6.19B).
intervillous space
This membrane, which is at
Cytotrophoblast
first 0 . 0 2 5 m m t h i c k , is
Capillary in villus r e d u c e d ro 0 . 0 0 2 m m .
Fetal blood vessels in However, towards the end of
extra-embryonic mesoderm pregnancy, a fibrinoid
d e p o s i t a p p e a r s on the
Fig. 6.14 Formation of cytotrophoblastic shell. Note that after
membrane, and this reduces
formation of this shell the syncytiotrophoblast is no longer in
contact w i t h maternal tissues.
its efficiency.
Functions of Placenta
Maternal surface
1 1. The placenta enables the
a - ^ ^ ^ ^ ^ ^ ^ ^ n _
t r a n s p o r t of o x y g e n ,
water, electrolytes and
nutrition (in the form of
carbohydrates, lipids,
f W Ramus ^ - ^ ^ JFRamuli y\g J^. polypeptides, amino acids
^ ^ M chorii ^k and vitamins) from
^M Truncus Mi Intervillus mp ^^L maternal to fetal blood. A
chorii ""•"' space ~~~f~^. ^ ^ full term fetus takes up
about 25 ml of oxygen per
m i n u t e from m a t e r n a l
b l o o d . Even a s h o r t
Fetal surface i n t e r r u p t i o n of oxygen
Umbilical cord
s u p p l y is fatal for t h e
fetus.
Fig. 6.15 Arrangement of anchoring villi and intervillous spaces within
the placenta. Note the subdivisions of each anchoring illus. 2. It a l s o p r o v i d e s for
e x c r e t i o n of c a r b o n
i n t e r c h a n g e s of o x y g e n , n u t r i t i o n a n d w a s t e dioxide, urea and other
products take place through this membrane. waste products produced by the fetus into
the maternal blood.
The total area of this membrane varies from 4 3. Maternal antibodies (IgG, gamma globulins
t o 14 square metres. It is interesting to note or I m m u o g l o b u l i n s ) reaching the fetus
that this is equal to the total absorptive area of through the placenta give the fetus immunity
the adult intestinal tract. As in the gut, the against some infections (e.g. diphtheria and
effective absorptive area is greatly increased measles).
by the presencejpf numerous microvilli on the 4. The placenta acts as a barrier and prevents
surface of the syncytiotrophoblast. many bacteria and other harmful substances
In the later part of pregnancy, the efficiency from reaching the fetus. However, most
Human Embryology
Umbilical cord
Fig. 6.17 Structure of a fully formed placenta. Each lobe (labelled cotyledon) contains a number of
anchoring villi but only one is shown here for the sake of simplicity.
The Placenta
Somatomammotropin (bCS) h a s an a n t i -
insulin effect on the mother leading to increased
plasma levels of glucose and amino acids in
t h e m a t e r n a l c i r c u l a t i o n . In t h i s w a y it
increases availability of these materials for the
fetus. It also enhances glucose utilization by
the fetus.
— Upper uterine
segment
Vagina
Intervillus space
Umbilical cord
2. lobed, w h e n it is d i v i d e d i n t o l o b e s
(Fig.6.24B);
3. diffuse, when chorionic villi persist all round
the blastocyst: the placenta is thin and does
not assume the shape of a disc (Fig. 6.24C);
4. placenta succenturiata, when a small part
of the placenta is separated from the rest of
it (Fig. 6.24D);
5. fenestrated, when there is a hole in the disc
(Fig. 6.24E); and
6. ctrcumvallate, when the peripheral edge of
Fig. 6.23 Abnormal sites of implantation: the placenta is covered by a circular fold of
(1) Normal site, (2) Placenta praevia, decidua (Fig. 6.24F).
(3) Interstitial tubal implantation,
(4) Tubal implantation, (5) A b d o m i n a l The umbilical cord is normally attached to the
implantation, (6) O v a r i a n implantation. placenta near the centre (Fig. 6.25A). However,
this attachment may be:
Implantation outside the Uterus
When the ovum gets implanted at any site outside
the uterus, this is called an ectopic pregnancy. This
may be as follows:
Fig. 6.25 Variations in attachment of umbilical cord t o placenta: (A) N o r m a l , (B) M a r g i n a l . (C) Furcate,
(D) Velamentous insertion.
Amniotic cavity
Decidua / /*
parietalis / /
Decidua basalts
Chorion / \ \ Decidua
(pink) / / \ \ ^ basalis
^ A \ V— Placenta
/ 1
(
s
Amniotic cavity j f 1 J
Amnion X.
(blue)
Uterine / / Decidua
cavity / / parietatis
Fig. 6.27 Relationship of amniotic cavity and uterine cavity after obliteration
o f the extra-embryonic c o e l o m .
Human Embryology
aspects of the process of childbirth. The changing membrane. From Fig. 6.27 it will be seen that the
relationships will be best u n d e r s t o o d by first wall of the amniotic cavity is now formed by (i)
reviewing Figs 4.6, 4.7 and 4.13 and then by amnion, (ii) chorion, and (Hi) decidua capsularis,
studying Figs 6 . 2 6 - 6 . 2 8 . all three being fused t o one another.
In Fig. 6.26 we see three cavities, namely, the Further expansion of the amniotic cavity occurs
uterine cavity, the extra-embryonic coelom, and at the expense of the uterine cavity. Gradually,
the amniotic cavity. The outer wall of the extra- the decidua capsularis fuses with the decidua
embryonic coelom is formed by chorion and the parietalis, and the uterine cavity is also obliterated
inner wall by a m n i o n . As the amniotic cavity (Fig. 6.28). Still further expansion of the amniotic
enlarges, the extra-embryonic coelom becomes cavity is achieved by enlargement of the uterus.
smaller and smaller. It is eventually obliterated, H n l a r g e m e n t of t h e a m n i o t i c c a v i t y is
by fusion of a m n i o n and c h o r i o n . T h e fused accompanied by an increase in the a m o u n t of
chorion and amnion form the amniochorionic amniotic fluid.
At the time of parturition (childbirth), the fused transferred through the placenta to maternal
amnion and chorion (amniochorionic membrane) blood. When the fetal kidneys start working
(along with the greatly thinned out decidua the fetus passes urine into the amniotic fluid.
capsularis), constitute what are called the This does not cause harm because fetal urine is
membranes. As the uterine muscle contracts, made up mostly of water (metabolic wastes
increased pressure in the amniotic fluid causes these being removed from blood by the placenta and
membranes to bulge into the cervical canal. This not through the kidneys).
bulging helps to dilate this canal. The bulging In some cases hydramnios is associated with
membranes can be felt through the vagina and atresia of the oesophagus, which prevents
are referred to as the bag of waters. Ultimately swallowing of amniotic fluid by the fetus.
the membranes rupture. Amniotic fluid flows out Oligamnios is sometimes associated with renal
into the vagina. After the child is delivered, the agenesis as no urine is added to the amniotic
placenta and the membranes, along with all parts fluid.
of the decidua, separate from the wall of the uterus
and are expelled from it.
TIMETABLE OF SOME EVENTS
DESCRIBED IN THIS CHAPTER
AMNIOTIC FLUID
Age (in Days) Developmental Events
Amniotic fluid provides support for the delicate 8th day Trophoblast differentiates
tissues of the growing embryo or fetus. It allows into cytotrophoblast and
free movement and protects the fetus from external
syncytiotrophoblast.
injury. It also avoids adhesion of the fetus to
amnion. As pregnancy advances the quantity of 9th day Lacunae appear in rhe
this fluid increases, till at full term it is about one syncytium.
litre. 11 th day Embryo gets completely
The condition in which there is too much implanted in the
amniotic fluid (over 1500 ml) is called endometrium.
hydramnios; and when the fluid is too little it is 13th day Primary villi are formed.
called oligamnios. Both conditions can cause 16th day Secondary and tertiary villi
abnormalities in the fetus. They can also cause are seen.
difficulties during childbirth. 2nd month Villi are seen all around the
trophoblast.
There is constant exchange of water between 4th month A definitive placenta is
the amniotic fluid and maternal blood, the water formed.
being completely replaced every three hours.
Some time in the fifth month the fetus begins to Full term Placenta is shed about half
swallow amniotic fluid. This fluid is absorbed an hour after birth of the
(through the gut) into fetal blood and is baby.
Chapter
The human body is made up of many types of external acoustic meatus and outer surface
tissue. These are k n o w n as basic tissues of the of tympanic membrane.
body. They are as follows: 3. Epithelium of some parts of the mouth, lower
part of anal canal, terminal part of male
Epithelial Tissue urethra, parts of female external genitalia.
Epithelium consists of cells arranged in the form
Some Epithelia derived from Endoderm
of continuous sheets. Epithelia line the external
and internal surfaces of the body and of body 1. Epithelium of the entire gut except part of
cavities. t h e m o u t h a n d a n a l c a n a l (lined by
ectoderm).
Connective Tissue 2. Epithelium of auditory tube and middle ear.
Connective tissue proper includes loose connective 3. Epithelium of respiratory tract.
tissue, dense connective tissue and adipose tissue. 4. Epithelium over part of urinary bladder,
Blood, cartilage and bone are special connective urethra and vagina.
tissues.
Some Epithelia derived from Mesoderm
Muscular Tissue 1. Tubules of kidneys, ureter, trigone of urinary
bladder.
This is of three types: striated, cardiac and smooth.
2. Uterine tubes, uterus, part of vagina.
Nervous Tissue 3. Testis and its duct system.
4. Endothelium lining the heart, blood vessels
This tissue consists of neurons (nerve cells), nerve
and lymphatics.
cell processes (axons and dendrites) and cells of
5. M e s o t h e l i u m l i n i n g t h e p e r i c a r d i a l ,
neuroglia.
peritoneal and pleural cavities; and cavities
In this chapter we shall study the formation of
of joints.
these basic tissues.
GLANDS
EPITHELIA
Almost all glands, both exocrine and endocrine,
An epithelium may be derived from ectoderm, develop as diverticula from epithelial surfaces
endoderm or mesoderm. In general, ectoderm gives (Fig. 7.1A}. T h e gland may be derived from
rise to epithelia covering the external surfaces of elements formed by branching of one diverticulum
the body; and some surfaces near the exterior. (e.g. p a r o t i d ) or may be formed from several
Endoderm gives origin to the epithelium of most diverticula (e.g. lacrimal gland, prostate). The
of the gut; and of structures arising as diverticula opening of the duct (or ducts) is usually situated
from t h e g u t (e.g. t h e liver a n d p a n c r e a s ) . at the site of the original outgrowth. In the case of
Mesoderm gives origin to the epithelial lining of endocrine glands (e.g. thyroid, anterior part of
the greater part of the urogenital tract. hypophysis cerebri) the gland loses all contact with
the epithelial surface from which it takes origin.
Some Epithelia derived from Ectoderm The diverticula are generally solid to begin with
1. Epithelium of skin, hair follicles, sweat (Figs 7.1 A, B) and are canalized later (Fig. 7.1C).
glands, sebaceous glands, and m a m m a r y The proximal parts of the diverticula form the
glands. duct system. The distal parts of the diverticula
2. Epithelium over cornea and conjunctiva, form the secretory elements (Fig. 7.1D).
Human Embryology
T
Solid downgrowth from epithelium Branching of downgrowth
MESENCHYME
We have seen above that a small proportion of
m e s o d e r m a l cells give rise to e p i t h e l i a . T h e
r e m a i n i n g cells, t h a t m a k e up t h e bulk of
mesoderm, get converted into a loose tissue called
mesenchyme (Fig. 7.2). Mesenchymal cells have
the ability to form many different kinds of cells
that in turn give rise t o various tissues (Fig. 7.3).
Chondroblasts arising from m e s e n c h y m a l Fig. 7.2 Mesenchymal cells. Note the delicate
cells form c a r t i l a g e , osteoblasts form b o n e , cytoplasmic processes j o i n i n g the cells
myoblasts form muscle, while lymphoblasts and t o one another.
Formation of Tissues of the Body
- -M~ Osteocyte
Precursors of
celts of blood
Lymphoblast
haemocytoblasts form various cells of blood. In the third week of embryonic life, formation
Mesenchymal cells also give rise to endothelial of blood vessels and blood cells is first seen in the
cells from which blood vessels and the primitive w a l l of t h e y o l k s a c , a r o u n d t h e a l l a n t o i c
heart tubes are formed. However, after all these diverticulum and in the connecting stalk. In these
tissues have been formed many mesenchymal cells situations, clusters of mesodermal cells aggregate
are still left and they give rise to cells of various to form blood islands. These mesodermal cells are
types of connective tissue. then converted to precursor cells (haemangioblasts)
which give rise t o blood vessels and blood cells
(Fig. 7.4). Cells, which are present in the centre of
CONNECTIVE TISSUE
the blood island, form the precursors of all blood
As the name suggests, connective tissue serves as cells [haematopoietic stem cells). Cells at the
a connecting system binding, s u p p o r t i n g a n d periphery of the island form the precursors of blood
strengthening all other body tissues together. vessels (angioblasts).
Connective tissue consists of three components,
i.e. cells, fibres and ground substance.
The fibres and ground substance are Cubical cells lining the
s y n t h e s i z e d b y t h e c e l l s of t h e secondary yolk sac
connective tissue. Splanchnopleuric
extra-embryonic
Formation of Loose mesoderm
Connective Tissue Mesodermal cells
forming blood island
At the site of f o r m a t i o n of loose
connective tissue the mesenchymal
cells get converted into fibroblasts.
Fibroblasts secrete the g r o u n d
substance and synthesize the collagen, Epithelium lining
the yolk sac
r e t i c u l a r a n d clastic fibres. Some
m e s e n c h y m a l cells p r e s e n t in the
developing connective tissue also get Mesodermal cells of
blood island become
converted into histiocytes, mast cells, haemangioblasts
plasma cells and fat cells (Fig. 7.3).
FORMATION OF BLOOD
Blood is a specialized fluid connective
tissue, which acts as a major transport
system within the body. The formation Endothelial cells
of the cells of blood begins very early
in embryonic life (before somites have
appeared) and continues throughout
life. Blood formation is specially rapid
in the embryo to provide for increase
in blood volume with the growth of Fig. 7.4 Formation of blood cells and b l o o d vessel from a
the embryo. b l o o d island.
Formation of Tissues of the Body
Blood cells arising in the blood islands of the mesoderm surrounding the developing aona. These
yolk sac are temporary. They are soon replaced stem cells first form colonies in the liver.
by permanent stem cells, which arise from the In the late embryonic period the formation of
T-CELL
/ X T-LYMPHOCYTES
PRECURSOR
/
[
TOTIPOTENT \
HAFMAI ] „
PLEURIPOTENT
LYMPHOID
*-
STEM CELLS
B-CELL
\ (THSC) / (PLSC) B-LYMPHOCYTES
PRECURSOR
•
/ PLEURIPOTENA
HAEMAL
\ STEM CELL /
\ (PHSC) /
Fig. 7.5 Scheme showing the terms applied to precursors of various blood cells. CFU = Colony Forming
Unit. BFU = Burst Forming Unit. Note the other abbreviations used for other precursor cells.
Human Embryology
FORMATION OF CARTILAGE
Cartilage is formed from mesenchyme. At a site Between adjoining lamellae there are spaces
called lacunae. These spaces are occupied by
where cartilage is to be formed, mesenchymal cells
cells of bone (osteocytes).
b e c o m e c l o s e l y p a c k e d . T h i s is c a l l e d a
mesenchymal condensation. The mesenchymal
cells then become rounded and get converted into
cartilage forming cells or chondroblasts (Fig. 7.3).
U n d e r t h e i n f l u e n c e of c h o n d r o b l a s t s , t h e
intercellular substance of cartilage is laid down.
Some chondroblasts get imprisoned within the
substance of this developing cartilage and arc
called chondrocytes. Some fibres also develop in
the intercellular substance. In hyaline cartilage,
collagen fibres are present, but are not seen easily. Fig. 7.6 Scheme to show that bone is made up of
In fibrocartilage, collagen fibres are numerous and lamellae.
Formation of Tissues of the Body
Cells of Bone
Three main types of cells present in bone are as
follows:
Osteocytes are cells that are seen in mature
bone.
Capillaries in bone marrow
Osteoblasts are bone forming cells. These
cells are, therefore, seen wherever bone is
Fig. 7.7 Osteocytes placed amongst lamellae of bone. being laid down. They have abundant
Bony trabeculus
Marrow cavity
;-*:
- Haversian system
•us i ^ j y .
B
Fig. 7.8 (A) Structure of spongy bone. (B) Structure of compact bone.
Human Embryology
~w&^ \
Osteoclasts
^
(/~~ bones. In some situations (e.g. the vault
of the skull) formation of bone is not
preceded by formation of a cartilaginous
model. Instead, bone is laid down directly
in a fibrous membrane. This is called
removing bone intramembranous ossification and these
bones are called membrane bones. These
Fig. 7.9 Relationship of osteoblasts and osteoclasts to include the bones of the vault of the skull,
developing bone. the mandible and the clavicle.
f |I |
1 ill
SQB
&&&$
A B C D
Fig. 7.10 Endochondral ossification: Formation of cartilaginous m o d e l .
P = Perichondrium; ECC - Enlarged cartilage cells.
Formation of Tissues of the Body
Osteoid (layer 1) -
1st lamellus
2nd (amellus-
Osteoid (layer 2)
Osteoid (layer 3) -
" Osteocyle —
/ •* Cartilaginous model
! _
I
/ Cartilaginous model
has grown larger.
Mesenchymal
condensation flEK/l Rone formation has
B M f i j ^ — — extended towards the
ffifll ends from primary centre.
Cartilage formed
by conversion of
mesenchymal cells
to cartilage cells
completely surrounds the cartilaginous shaft (Fig. 7.16A). At varying times after birth,
and is, therefore, called the periosteal collar secondary centres of e n d o c h o n d r a l
(Fig. 7.15). It is first formed only around ossification appear in the cartilages forming
the region of the primary centre but rapidly the ends of the bone (Fig. 7.16B). These
e x t e n d s t o w a r d s t h e e n d s of t h e centres enlarge until the ends become bony
cartilaginous model. The periosteal collar (Fig. 7 . 1 6 C ) . M o r e than one secondary
acts as a splint and gives strength to the centre of ossification may appear at either
cartilaginous model, at the site where it is end. The portion of bone formed from one
weakened by the formation of secondary secondary centre is called an epiphysis.
areolae. We shall see that most of the shaft
of the bone is derived from this periosteal For a considerable time after birth, the bone of
collar and is, therefore, intramembranous the diaphysis and the bone of the epiphysis are
in origin. s e p a r a t e d by a p l a t e of c a r t i l a g e called the
At about the time of birth, the developing epiphyseal cartilage, or epiphyseal plate. This is
bone consists of a part called the diaphysis formed by cartilage into which ossification has
(or shaft) (that is bony, and has been formed not extended either from the diaphysis or from the
by e x t e n s i o n of the p r i m a r y c e n t r e of epiphysis. We shall see that this plate plays a vital
ossification}; and ends that are cartilaginous role in growth of the bone.
Metaphysis
Diaphysis —*-
Marrow
cavity
Layer 2 removed
Periosteal bone
Endochondral bone
Layer 3
Layer 4 deposited
Layer 3 removed
Layer 4
Layer 5 deposited
Layer 3 deposited
Fig. 7.17 Formation of a typical long bone: Increase in thickness. Note that the shaft is ultimately made up
almost entirely of periosteal bone formed by the process of intramembranous ossification.
Human Embryology
Size after
some growth
Bone of
Formed by
epiphysis
!• growth
of cartilage
Bone of
diaphysis
On the other hand, bone grows only by localised to a particular part of the skeleton, or
deposition of more bone on its surface, or at its may be generalised. Anomalies of individual parts
ends. This is called appositional growth. of the skeleton are considered in Chapter 10. Some
anomalies that affect the skeleton as a whole are
Remodelling as follows:
We have seen above that when a tissue grows by
interstitial growth it is easy for it to maintain its 1. Disorderly and excessive proliferation of
shape. However, this is not true of bone, which cartilage cells in the epiphyseal plate, or
can grow only by apposition. This will be clear the failure of normally formed cartilage to
from Fig. 7.20. In this figure the brown line be replaced by bone, leads to the formation
represents the shape of a bone end. The green line of irregular masses of cartilage within the
represents the same bone end after it has grown metaphysis. This is called dyschondroplasia
for some time. It will be clear that some areas of or enchondromatosis.
the original bone have to disappear if proper shape 2. Abnormal masses of bone may be formed
is to be maintained. This process of removal of in the region of the metaphysis and may
unwanted bone is called remodelling. protrude from the bone. Such a protrusion
The trabeculae of spongy bone and the is called an exostosis, and the condition is
Haversian systems of compact bone are so called multiple exostoses or diaphyseal
arranged that they are best fitted to bear stresses aclasis. This condition may be a result of
interference with the process of remodelling
imposed on them. This arrangement can change
of bone ends.
with change in stresses acting on the bone. This
process is often called internal remodelling. 3. Calcification of bone may be defective
[osteogenesis imperfecta) and may result in
multiple fractures.
4. Parts of bone may be replaced by fibrous
Bone and cartilage formation may sometimes be tissue {fibrous displasia).
abnormal as a result of various genetic and 5. Bones may show increased density or
environmental factors. The anomalies may be osteosclerosis. One disease characterised by
increased bone density is known as
osteopetrosis, or marble bone disease.
Early outline 6. In the condition called achondroplasia, there
of bone end
Area of bone that is insufficient, or disorderly, formation of
needs to be removed bone in the region of the epiphyseal
to maintain shape
of bone cartilage. This interferes with growth of long
bones. The individual does not grow in
height and becomes a dwarf. A similar
condition in which the limbs are of normal
length, but in which the vertebral column
remains short, is called chondro-osteo-
dystrophy.
7. Anomalous bone formation may be confined
to membrane bones. One such condition is
cleido-cranial dysostosis in which the
Fig. 7.20 Remodelling of bone ends during clavicle is absent and there are deformities
growth. of the skull. On the other hand, anomalies
Human Embryology
Surface ectoderm
Myotome
Spinal nerve
Myotome
Epidermis derived
Cells of the dermatome from surface ectoderm
migrate to the surface
and form the dermis
of the skin.
Epimere
• innervated by Myotome gives
dorsal ramus origin to muscles
Fig. 7.21 (A) Somites lying on either side of the neural tube. Note subdivisions of somite.
(B) The cells of the sclerotome have migrated medially and n o w surround the neural tube.
The myotome is innervated by nerves growing out of the neural tube. (C) The cells of the
dermatome have migrated to form the dermis of the skin.
Formation of Tissues of the Body
Germinal layer
Mantle layer ^
Fig. 7.22 Layers of the neural tube. Although the germinal (neuroepithelial) layer is shown as a simple
epithelium it is actually pseudostratified.
Formation of Tissues of the Body
A
s> Apolar
neuroblast
Multipolar T*_
0 neuroblast
D
\ Unipolar
/ ~ neuroblast
C
<y-
Fig. 7.23 Stages in formation of a typical neuroblast.
One of the germinal cells passes from the The process of the cell which does not
germinal layer to the mantle layer and disappear now elongates, and on the side
becomes an apolar neuroblast {Fig. 7.23A). opposite to it numerous smaller processes
Two processes develop and convert the form. At this stage the cell is called a
apolar neuroblast to a bipolar neuroblast multipolar neuroblast (Fig. 7.23D).
(Fig. 7.23B). The main process of the multipolar
One of the processes of the neuroblast neuroblast now grows into the marginal
disappears, and it can now be called a layer, and becomes the axon of the nerve
unipolar neuroblast (Fig. 7.23C). cell (Fig. 7.22C). The axon can grow to a
HIGHLIGHTS
• The epidermis is derived from surface ectoderm.
• The dermis is formed by mesenchyme derived
from dermatomes of somites.
• Naib develop from ectoderm at the tip of each
digit. Later this ectoderm migrates to the dorsal
aspect.
• Hair are derived from surface ectoderm that is
modified to form hair follicles.
• Sebaceous glands (ectoderm) arise as diver-
ticula from hair follicles.
• Sweat glands develop as downgrowths from
the epidermis, which are later canalized.
• Mammary glands arise from surface ectoderm.
They are formed along a milk line extending
from axilla to the inguinal region.
SKIN
Surface ectoderm
forms epidermis -
Neural crest
gives rise to
dendritic cells.
Dermatome of somite
forms the dermis.—
Myotome
Epidermis
Sebaceous
gland
. Developing
hair
- Papilla
Germinal
layer
-Bud for
sebaceous gland
- Papilla
-Papilla E
form the root of the nail. Here the cells of the SEBACEOUS GLANDS
germinal layer multiply to form a thick layer of
cells called the germinal matrix. As the cells in A sebaceous gland is formed as a bud arising from
this matrix multiply, they are transformed into ectodermal cells forming the wall of a hair follicle.
the nail suhstance which corresponds to the stratum Some stages in the formation of a sebaceous gland
lucidum of the skin (Fig. 8.3). are shown in Figs 8.4C to E.
The migration of the primary nail fields from
the tips of the digits to their dorsal aspect explains SWEAT GLANDS
why the skin of the dorsal aspect of the terminal
part of the digits is supplied by nerves of the ventral A sweat gland develops as a downgrowth from
aspect. the epidermis (Fig. 8.5A). The downgrowth is at
first solid but is later canalized. The lower end of
HAIR the downgrowth becomes coiled (Fig. 8.5B} and
forms the secretory part of the gland.
The hair are also derived from surface ectoderm.
At the site where a hair follicle is to form, the
Anomalies of Skin and its Appendages
germinal layer of the epidermis proliferates to form
a cylindrical mass that grows down into the dermis 1. Albinism: Absence of pigment in skin, hair
(Figs 8.4A, B). The lower end of this downgrowth and eyes occurs because melanocytes are
becomes expanded and is invaginated by a unable to synthesize melanin. In this
condensation of mesoderm, which forms the autosomal recessive genetic condition, skin
papilla (Figs 8.4C, D). The hair itself is formed is depigmented all over the body. This
by proliferation of germinal cells overlying the should be distinguished from vitiligo
papilla. As the hair grows to the surface, the cells which is not congenital. In vitiligo the
forming the wall of the downgrowth surround it absence of pigment is patchy. In the
and form the epithelial root sheath. An additional affected areas there is degeneration of
dermal root sheath is formed from the surrounding already existing melanocytes. It is an
mesenchymal cells. A thin band of smooth muscle autoimmune disease.
{arrector pili ) is formed by mesodermal cells. It 2. Aplasia: The skin may fail to develop in
gets attached to the dermal root sheath. A typical certain regions.
hair follicle is thus formed (Fig. 8.4E).
_
MO
I
for sweat gland _ ,
secretory part
,pL B
er
Fig. 8.5 Development of a sweat gland.
Human Embryology
MAMMARY GLANDS
In some animals (e.g. bitches} a series of
mammary glands are present on either side of the
midline, on the ventral surface of the trunk. These
are situated along a line that extends from the
Fig. 8.6 The mammary line passing from the
axilla to the inguinal region. In the human embryo,
axilla t o the inguinal region.
the ectoderm becomes thickened along this line to
form mammary ridges or lines
(Fig. 8.6). Most of this line soon
disappears. Each mammary gland
develops from a part of this line
that overlies the pectoral region.
In the region where the
mammary gland is to form, a
thickened mass of epidermal cells
is seen projecting into the dermis
(Fig. 8.7A). From this thickened
mass, sixteen to twenty solid
outgrowths arise and grow into the
B
W
surrounding dermis (Figs 8.7B, C).
The thickened mass of epidermis,
as well as these outgrowths, are
now canalized (Fig. 8.7D). The
secretory elements of the gland are
formed by proliferation of the
terminal parts of the outgrowths.
The proximal end of each
outgrowth forms one lactiferous Fig. 8.7 Stages in the development of the mammary gland.
The Skin and its Appendages
duct. The ducts at first open into a pit formed by opening into a pit. This causes difficulty
cavitation of the original epithelial thickening. in suckling.
However, the growth of underlying mesoderm 6. The gland may be abnormally small
progressively pushes the wall of this pit outwards, {micromastia) or abnormally large
until it becomes elevated above the surface and (macromastia).
forms the nipple (Fig. 8.7E). The mammary gland 7. Gynaecomastia: The male breast may
remains rudimentary in the male. In females, the enlarge as in the normal female and may
ducts and secretory elements undergo extensive even secrete milk.
development during puberty and pregnancy.
TIMETABLE OF SOME EVENTS
Developmental Anomalies of tin MENTIONED IN THIS CHAPTER
Mammary Glands
Age Developmental Events
1. Amostia: The gland may be absent on one
or both sides. 7th week Mammary line is
2. Athelia: The nipple may be absent. established.
3. Polythelia and polymastia: Supernume- 8th week Melanoblasts start
rary nipples may be present anywhere appearing.
along the milk line. They may remain 1st to 3rd month Cells of neural crest
rudimentary (polythelia) or may form migrate to skin.
accessory mammary glands (polymastia). 2nd month Surface ectoderm is single
4. Accessory breasts may be found away from layered.
the milk line. They have been observed in 2nd to 4th month Surface ectoderm becomes
the neck, cheeks, femoral triangle and
multiple layered.
vulva.
3rd to 4th month Dermal papillae are
5. Inverted or crater nipple: The nipple may
fail to form resulting in lactiferous ducts formed.
The Pharyngeal Arches
d e s t i n e d t o form t h e p h a r y n x ) , b e f o r e t h e
INTRODUCTION
appearance of the pharyngeal arches, is shown in
The formation of the foregut has been considered Fig. 9.2A. At this stage, the endodermal wall of
in Chapter 5. Reference to Fig. 5.14 will show the foregut is separated from the surface ectoderm
that after the establishment of the head fold, the by a layer of mesoderm. Soon, thereafter, the
foregut is bounded ventrally by the pericardium, mesoderm comes to be arranged in the form of six
and dorsally by the developing brain. Cranially, bars that run dorsoventrally in the side wall of the
it is at first separated from the stomatodaeum by foregut. Each of these 'bars' grows ventrally in
the b u c c o p h a r y n g e a l m e m b r a n e . W h e n this the floor of the developing pharynx and fuses with
membrane breaks down, the foregut opens to the the corresponding 'bar' of the opposite side to form
exterior through the stomatodaeum. a pharyngeal or branchial arch. In the interval
At this stage, the head is represented by the between any two adjoining arches, the endoderm
bulging caused by the developing brain (Fig. 5.14), e x t e n d s o u t w a r d s in t h e form of a p o u c h
while the p e r i c a r d i u m may be considered as {endodermal or pharyngeal pouch) to meet the
occupying the region of the future thorax. The ectoderm which dips into this interval as an
two are separated by the stomatodaeum which is ectodermal cleft (Fig. 9.2B).
the future mouth. It is, thus, apparent that a neck The first arch is also called the mandibular arch;
is not yet present. and the second, the byoid arch. The third, fourth
The neck is formed by the elongation of the and sixth arches do not have special names. The
region between the stomatodaeum and the pericar- fifth arch disappears soon after its formation, so
dium. This is achieved, partly, by a 'descent' of that only five arches remain.
the developing heart. 1 lowcver, this elongation is T h e following structures are formed in the
due mainly t o the a p p e a r a n c e of a series of mesoderm of each arch (Fig. 9.3):
mesodermal thickenings in the wall of the cranial-
most part of the foregut. These are called the I. A skeletal element: This is cartilaginous to
pharyngeal or branchial arches (see Fig. 9.1). begin with. It may remain cartilaginous,
A coronal section through the foregut (the part may develop into bone, or may disappear.
Bulging produced by
developing brain Pharyngeal arches
Pharyngeal arches
Stomal od aeum'J
Hindlimb
bud
Foreiimb
Pericardial bulge
bud
Fig. 9.1 Lateral views of embryos showing the formation of pharyngeal arches between stomatodaeum
and the pericardial bulge.
Human Embryology
Buccopharyngeal
membrane
Ectoderm (blue)
Primitive pharynx
derived from Endoderm (red)
foregut
Mesoderm (green)
Buccopharyngeal membrane
disappears.
Fig. 9.2 Coronal sections through cranial part of foregut. (A) Before, and (B) After
formation of pharyngeal arches.
2. Striated muscle: This is supplied by the nerve with them, and their embryological
nerve of the arch. In later development, this origin can thus be determined from their
musculature may, or may not, retain its nerve supply.
attachment to the skeletal elements derived An arterial arch: Ventral to the foregut, an
from rhe arch. It may subdivide to form a artery called the ventral aorta develops.
number of distinct muscles, which may Dorsal to the foregut, another artery called
migrate away from the pharyngeal region. the dorsal aorta, is formed. A series of
When they do so, however, they carry their arterial arches [aortic arches) connect the
The Pharyngeal Arches
ventral and dorsal aortae. One such arterial In some lower animals, each arch is supplied
a r c h lies in e a c h p h a r y n g e a l a r c h . In by t w o nerves (Fig. 9.4). The nerve of the arch
subsequent development, the arrangement itself runs along the cranial border of the arch.
of these arteries become greatly modified. This is called the post-trematic nerve of the arch
The fate of the arterial arches is considered (trema • trench). Each arch also receives a
in Chapter 15. branch from the nerve of the succeeding arch.
This runs along the caudal border of the arch,
Each pharyngeal arch is supplied by a nerve. and is called the pre-trematic nerve of the arch.
In addition to supplying the skeletal muscle of the In the h u m a n e m b r y o , however, a d o u b l e
arch, it supplies sensory branches to the overlying i n n e r v a t i o n is to be seen only in the first
ectoderm and endoderm (Fig. 9.3). pharyngeal arch.
DERIVATIVES OF THE
SKELETAL ELEMENTS
1. T h e cartilage of the first arch is called
Meckel's cartilage (Fig. 9.5). The incus wad
malleus (of the middle ear) are derived from
its dorsal e n d . T h e ventral p a r t of the
cartilage is surrounded by the developing
mandible and is absorbed. The part of the
cartilage extending from the region of the
middle ear t o the mandible disappears, but
its sheath (perichondrium) forms the anterior
ligament of the malleus and the
sphenomandibular ligament.
M e s e n c h y m e of the first arch is also
responsible for formation of bones of the
face including the maxilla, the mandible,
the zygomatic bone, the palatine bone and
Fig. 9.3 Structures to be seen in a pharyngeal part of the temporal bone. (Also see first
arch. arch syndrome.)
Nerve I
Pre-trematic branch
" Nerve II
Post-trematic branch
Nerve III
Fig. 9.4 Arrangement of nerves supplying the pharyngeal arches in some lower animals.
Human Embryology
Spine of sphenoid
Stapes
Malleus
Styloid process
Sphenomandibular
ligament
Remnants of
Meckel's cartilage
within mandible
Greater cornu
Cricoid cartilage
Fig. 9.5 Fate of the cartilages of the pharyngeal arches. The left half of the figure
shows an earlier stage of development. The derivatives of the first arch
are shown in red, second arch in green, third arch in orange, and
fourth, fifth and sixth arches in blue.
T h e cartilage of the second arch forms the (e) Superior parr of body of hyoid bone.
following: (Note that all structures listed start with 'S').
(a) Stapes. The following structures are formed from
(b) Styloid process. the cartilage of the third arch:
(c) Stylohyoid ligament (from sheath). (a) Greater Cornu of hyoid bone.
(d) Smaller (lesser) cornu of hyoid bone. (b) Lower part of the body of hyoid bone.
The Pharyngeal Arches
4. The cartilages of the larynx are derived from while the chorda tympani (branch of facial nerve)
the fourth and sixth arches with a possible is the pre-trematic nerve. This double innervation
contribution from the fifth arch, but their is reflected in the nerve supply of the anterior two-
exact derivation is controversial. third of the tongue which is derived from the ventral
part of the first arch.
NERVES AND MUSCLES
OF THE ARCHES Some recent investigations suggest that
mesenchyme giving rise to muscles of the
All the muscles derived from a pharyngeal arch pharyngeal arches is derived from paraxial
are supplied by the nerve of the arch and can, mesoderm that is cranial to the occipital somites
therefore, be identified by their nerve supply. The (i.e. from the region of the pre-occipital
nerves of the arches and the muscles supplied by somites); and that its organization is influenced
them are given in Table 9.1. by neural crest cells. Although paraxial
mesoderm here does not form typical somites,
Table 9.1 Nerves of pharyngeal arches and it shows partial segmentation into seven masses
muscles supplied by them of mesenchyme called somitotneres. The
structures derived from the seven somitomeres
Arch Nerve of Arch Muscles of Arch and from five occipital somites that follow them,
Mandibular Medial and lateral have been described as given in Table 9.2.
pterygoids, Masseter,
Temporalis,
Mylohyoid, Anterior Table 9.2 Muscles derived from somitomeres and
belly of digastric, somites
Tensor tympani,
Tensorpalati. Somitomere/Somites Muscles Derived
If we accept this view of the origin of branchial swellings that lie in the neck, along the anterior
m u s c u l a t u r e , there would be n o significant border of the sternocleidomastoid. These are called
reason to distinguish between it and muscle branchial cysts, and are most commonly located
derived from somites. just below the angle of the mandible. If such a
cyst opens onto the surface, it becomes a branchial
sinus. Rarely, a cervical sinus may open into the
FATE OF ECTODERMAL CLEFTS lumen of the pharynx in the region of the tonsil.
After the formation of the pharyngeal arches, the
region of the neck is marked on the outside by a FATE OF ENDODERMAL POUCHES
series of grooves or ectodermal clefts. T h e dorsal
part of the first cleft (between the first and second T h e e n d o d e r m a l p o u c h e s t a k e p a r t in t h e
arches) develops into the epithelial lining of the formation of several important organs (Fig. 9.7).
external acoustic meatus. The pinna (or auricle) These are listed below.
is formed from a series of swellings or hillocks,
that arise on the first and second arches, where First Pouch
they adjoin the first cleft (for the development of (a) Its ventral part is obliterated by formation
the pinna refer to Chapter 19). T h e ventral parr of of the tongue.
this cleft is obliterated. (b) Its dorsal part receives a contribution from
The second arch grows much faster than the the dorsal part of the second pouch, and
succeeding arches and comes to overhang them these two together form a diverticulum that
(Fig. 9.6). T h e space between the overhanging grows t o w a r d s the region of the developing
second arch and the third, fourth and sixth arches ear. This diverticulum is called the tubo-
is called the cervical sinus. Subsequently, the lower tympanic recess. The proximal part of this
overhanging border of the second arch fuses with r e c e s s g i v e s rise t o t h e auditory
tissues caudal to the arches. The side of the neck (pharyngotympanic) tube and the distal part
(which was so far marked by the ectodermal clefts) to the middle ear cavity, including the
now becomes smooth. The cavity of the cervical tympanic antrum.
sinus (which is lined by ectoderm) normally gets
obliterated. Part of it may persist and give rise to Second Pouch
(a) T h e e p i t h e l i u m of t h e
ventral part of this pouch
contributes to the forma-
tion of the tonsil.
(b) The dorsal part takes part
Cervical sinus in the formation of the
lying deep to tubotympanic recess.
downward projection
Projection growing
downwards from Third Pouch
second arch
This gives rise to the inferior
parathyroid glands, a n d the
thymus.
Fourth Pouch
Fig. 9.6 Cervical sinus. The left half of the figure shows an earlier
stage than the right half. This gives origin to the superior
The Pharyngeal Arches
Tubotympanic recess
Tonsil
Parathyroid II
Parathyroid IV
Thymus
Fig. 9.7 Scheme to show the fate of the pharyngeal pouches (numbered 1 to 4).
parathyroid glands, and may contribute to the Early in development, this pouch is cut off, both
thyroid gland. from the pharyngeal wall and from the surface
ectoderm.
Fifth or Ultimobranchial Pouch After separation from the inferior parathyroid
A fifth pouch is seen for a brief period during rudiment, each thymic rudiment has a thinner
development. In some species it gives rise to the cranial part and a broader caudal part. The thinner
ultimobranchial body. Its fate in m a n is portion forms the cervical part of the thymus. The
c o n t r o v e r s i a l . It is generally believed t o be broader parts, of the two sides, enter the thorax and
i n c o r p o r a t e d into the fourth p o u c h , the t w o become united to each other by connective tissue.
together forming the caudal pharyngeal complex. Theendodermal cells of the thymus are invaded
The superior parathyroid glands arise from this by vascular mesoderm which contains numerous
complex. The complex probably also gives origin lymphoblasts. This invading mesenchyme partially
to the parafollicular cells of the thyroid gland. breaks up the thymic tissue into isolated masses,
and thus gives the organ its lobulated appearance.
DEVELOPMENT OF THE THYMUS Fragmentation of the cervical part of the thymus
may give rise to accessory thymic tissue. Such
The thymus develops from the endoderm of the t i s s u e , p r e s e n t in r e l a t i o n t o t h e s u p e r i o r
third pharyngeal pouch (which also gives rise to parathyroid glands, is believed to arise from the
the inferior parathyroid glands). fourth pouch.
Human Embryology
Thyroid
gland
. Parathyroid III
Fourth pouch
Parathyroid IV
Fig. 9.8 Derivation of superior and inferior parathyroid glands. Note that the
relative position of parathyroid III and IV is reversed during development.
The Pharyngeal Arches
YwJ
o n e of t h e l o b e s
Fourth arch •^^^
(Figs9.11B,C).Itmay
Fifth arch has
disappeared.
Sixth arch
\ \ II o ^ Tracheal groove
have no connection
w i t h t h e rest of t h e
thyroid, and may
A / be divided into two or
Fig. 9.9 Floor of the pharynx showing the foramen caecum from \ more parts (Fig. 9.1 ID).
the thyroglossal duct arises. In extent, it may vary
from a s h o r t s t u m p
Site of foramen caecum (Fig. 9.11A) to a pro-
cess reaching the hyoid
Floor of bone (Fig. 9.11C).
pharynx Thyroglossal duct
2. T h e i s t h m u s m a y be
absent (Fig. 9.12A).
h- Thyroglossal
duct
Lateral thyroid (?)
3. O n e of the lobes of the
g l a n d m a y be v e r y
small (Fig. 9.12B), or
from 4th pouch
absent (Fig. 9.12C).
Thyroid developing
from thyroglossal duct B. Anomalies of Position
(Fig. 9.13)
Bifid lower end
^r 1. Lingual thyroid: T h e
thyroid may lie under
Fig. 9.10 Stages in the development of the thyroid gland.
t h e m u c o s a of t h e
the neck. Its tip soon bifurcates (Fig. 9.IOC). d o r s u m of the t o n g u e a n d m a y form a
Proliferation of the cells of this bifid end gives s w e l l i n g t h a t m a y c a u s e difficulty in
rise to the t w o lobes of the thyroid gland. swallowing.
The developing thyroid comes into intimate Intra-lingual thyroid: The thyroid may be
relationship with the caudal pharyngeal complex embedded in the muscular substance of the
and fuses with it (Fig. 9.10D). Cells arising from tongue.
this complex are believed to give origin to the Suprahyoid thyroid: The gland may lie in
parafollicular cells of the thyroid which may the midline of the neck, above the hyoid bone.
Human Embryology
Fig. 9.11 Variations in the pyramidal process Fig. 9.12 Anomalies of the thyroid gland. The
of the thyroid gland. parts of the gland shown in dotted
outline are missing.
4. Infrahyoid thyroid: The gland may lie below
the hyoid bone, but above its normal Tongue
position. Lingual thyroid
D. Remnants of the Thyroglossal Duct to be remembered that the duct is intimately related
to the hyoid bone (Fig. 9.13).
These r e m n a n t s m a y persist a n d lead t o t h e
formation of the following:
TIMETABLE O F S O M E EVENTS
1. Thyroglossal cysts, that may occur M E N T I O N E D IN THIS C H A P T E R
anywhere along the course of the duct. They
Age Developmental Events
may acquire secondary openings o n the
surface of the neck t o form fistulae. 4th week Appearance of 1st and 2nd
2. Thyroglossal fistula opening at the foramen (22nd day) arches.
caecum. 5th week Four arches are seen.
3. Carcinoma of the thyroglossal duct. (29th day) Thyroid, parathyroid and
thymus start forming.
In the surgical removal of thyroglossal cysts
7th week Thyroid gland reaches its
and fistulae, it is important to remove all remnants
of the thyroglossal duct. In this connection, it has definitive position.
The Skeleton
HIGHLIGHTS
• T h e vertebral column is derived from the
sclerotomes of somites. Each sclerotome divides
into three parts: cranial, middle and caudal.
• A vertebra is formed by fusion of the caudal
part of one sclerotome and the cranial part of
the n e x t s c l e r o t o m e . It is, t h e r e f o r e ,
intersegmental in position.
• The middle part of the sclerotome forms an
intervertebral disc, w h i c h is t h e r e f o r e
segmental in position.
• The sternum is formed by fusion of right and
left sternal bars.
• The skull develops from mesenchyme around
the developing brain. Some skull bones are
formed in m e m b r a n e (e.g. p a r i e t a l ) ; some
partly in membrane and partly in cartilage
(e.g. sphenoid); and a few entirely in cartilage The process of bone formation has been considered
(e.g. ethmoid). in Chapter 7. We have seen that all bone is of
m e s o d e r m a l o r i g i n , a n d t h a t b o n e s c a n be
• The mandible is formed in membrane from the classified as cartilage bones or membrane bones,
mesenchyme of the mandibular process.
on the basis of their mode of ossification. We shall
• Limbs are first seen as outgrowths {limb buds) now consider the development of some individual
from the side wall of the embryo. Each bud parts of the skeleton.
grows and gets subdivided to form parts of the
I i m b.
THE VERTEBRAL COLUMN
• Limb bones develop from mesenchyme of the
limb b u d s . Joints are formed in intervals T h e v e r t e b r a l c o l u m n is f o r m e d f r o m the
between bone ends. sclerotomes of the somites.
fe
Mesenchyme M ; . • ; v7 'Sclerotome
from
sclerotome Notochord '7
Mesenchymal basis - Notochord
of costal element
Fig. 10.1 Formation of mesenchymal basis of the
body of a vertebra from a sclerotome.
Mesenchymal basis
of vertebra! body
(Fig. 10.1). The mesenchyme then extends
backwards on either side of the neural tube and Fig. 10.2 Formation of mesenchymal basis of the
surrounds it (Fig. 10.2). Extensions of this neural arch and of the costal element.
mesenchyme also take place laterally in the
position to be subsequently occupied by the (Fig. 10.3A). The mesenchymal cells of each
transverse processes, and ventrally in the body segment are at first uniformly distributed.
wall, in the position to be occupied by the ribs. However, the cells soon become condensed in a
region that runs transversely across the middle of
For some time the mesenchyme derived from the segment. This condensed region is called the
each somite can be seen as a distinct segment perichordal disc. Above and below it there are
£ ^Vertebra
Intervertebral
disc
. Nucleus
pulposus
Caudal less t
condensed part
Fig. 10.3 (A) Mesenchyme derived f r o m somites is seen in the form of segments. (B) Each segment has a
central condensed part, and cranial and caudal less condensed parts. (C) A vertebra is formed by
fusion of adjoining uncondensed parts of t w o somites. Hence it is an intersegmental structure.
Each intervertebral disc is derived from the condensed part of one somite. Hence it is segmental
in position.
Human Embryology
less condensed parts (Fig. 10.3B). The mesenchy- neural arch and one for the greater part of the
mal basis of the body (or centrum) of each vertebra body (centrum). At birth the centrum and the
is f o r m e d by fusion of t h e a d j o i n i n g , less two halves of the neural arch are joined by
condensed parts of two segments (Fig. 10.3B). The c a r t i l a g e (Fig. 1 0 . 4 A ) . T h e s e a r e t e r m e d
perichordal disc becomes the intervertebral disc. neurocentral joints. Note that the posterolateral
parts of the vertebral body are formed from the
The neural arch, the transverse processes and neural arch (Fig. 10.4B). After the centrum and
the costal elements are formed in the same way neural arch have fused, the junction between
as the body. T h e interspinous and intertrans- the t w o is indicated by the neurocentral line.
verse ligaments are formed in the same manner
as the intervertebral disc.
Congenital Anomalies of
T h e notochord disappears in the region of
Vertebral Column
the vertebral bodies. In the region of the inter-
vertebral discs, the notochord becomes expand- O n e or more vertebrae may be absent, the
ed and forms the nucleuspulposus (Fig. 10.3C). caudal vertebrae being more commonly
affected. Absence of the coccyx alone, or
From the above account we may note that: of the sacrum and coccyx, may be seen.
Additional vertebrae may be present. The
1. T h e vertebra is an intersegmental structure sacrum may show six segments.
made up from portions of two somites. The Part of a vertebra may be missing. This
position of the centre of the somite is m a y r e s u l t in v a r i o u s a n o m a l i e s ,
represented by the intervertebral disc. depending on the part t h a t is absent.
2. The transverse processes and ribs are also
intersegmental. They separate the muscles (a) The two halves of the neural arch may
derived from two adjoining myotomes. fail t o fuse in t h e m i d l i n e . T h i s
3. Spinal nerves are segmental s t r u c t u r e s . c o n d i t i o n is c a l l e d spina bifida
They, therefore, emerge from between two (Fig. 10.5). T h e g a p b e t w e e n the
adjacent v e r t e b r a e and lie
between t w o adjacent ribs.
Part of vertebral body
4. The blood vessels supplying formed by neural arch
structures derived from the
m y o t o m e (e.g. i n t e r c o s t a l
vessels) are intersegmental
like the vertebrae. Therefore,
the intercostal and l u m b a r
a r t e r i e s He o p p o s i t e t h e
vertebral bodies.
T h e m e s e n c h y m a l basis of t h e
vertebra is converted into cartilage Neurocentral line
by t h e a p p e a r a n c e of s e v e r a l
centres of chondrification. Three Fig. 10.4 (A) A vertebra at birth consisting of three separate pieces
p r i m a r y centres of ossification of bone: a centrum and t w o neural arches. (B) Diagram
appear in the cartilaginous model to show the neurocentral line w h i c h is the line along
for each vertebra: one for each w h i c h body and neural arch have fused.
The Skeleton
THE STERNUM Fig. 10.6 Relative contribution to vertebrae by the centrum, the
neural arch and the costal element in different
The sternum is formed by fusion of two regions. Note that a small part of the body of the
sternal bars, or plates, that develop on vertebra is derived from the neural arch.
The Skeleton
in membrane; the rest of the bone is formed 5. The occipital bone may be fused to the
by endochondral ossification. atlas vertebra.
(b) Sphenoid: The lateral part of the greater 6. See mandibulo-facial dysostosis.
wing and the pterygoid laminae are formed
in membrane; the rest is cartilage bone. FORMATION OF THE LIMBS
(c) Temporal: The squamous and tympanic
parts are formed in membrane. The petrous The bones of the limbs, including the bones of the
and mastoid parts are formed by ossification shoulder and pelvic girdles, are formed from
of the cartilage of the otic capsule. The mesenchyme of the limb buds. With the exception
styloid process is derived from the cartilage of the clavicle (which is a membrane bone), they
of the second branchial arch. are all formed by endochondral ossification.
(d) Mandible: Most of the bone is formed in The limb buds are paddle-shaped outgrowths
membrane in the mesenchyme of the that arise from the side-wall of the embryo at the
mandibular process. The ventral part of beginning of the second month of intrauterine life
Meckel's cartilage gets embedded in the (Fig. 10.8). Each bud is a mass of mesenchyme
bone. The condylar and coronoid processes covered by ectoderm.
are ossified from secondary cartilages that
appear in these situations. At the tip of each limb bud, the ectoderm is
thickened to form the apical ectodermal ridge.
The development of the hyoid bone has been This ridge has an inducing effect on underlying
described in Chapter 9. mesenchyme causing it to remain undifferen-
tiated and to proliferate. Areas away from the
Anomalies o f the Skull ridge undergo differentiation into cartilage,
muscle, etc.
1. The greater part of the vault of the skull is
missing in cases of anencephaly.
The forelimb buds appear a little earlier than
2. The skull may show various types of defor-
the hindlimb buds. As each forelimb bud grows, it
mity. In one syndrome, deformities of the
skull are associated with absence of the
clavicle [cleidocranial dysostosis). Prema- Pharyngeal arches
ture union of the sagittal suture gives rise
to a boat-shaped skull {scaphocephaly).
Early union of the coronal suture results
in a pointed skull (acrocephaty).
Asymmetrical union of sutures results in a
twisted skull (plagiocephaly). When the
brain fails to grow the skull remains small
{microcephaly).
3. The bones of the vault of the skull may be
widely separated by expansion of the cra-
nial cavity in congenital hydrocephalus.
4. In a rare congenital condition called Hand-
Schuller-Christian disease, large defects
are seen in the skull bones. The primary
defect is in the reticuloendothelial system;
the changes in the bones are secondary. Fig. 10.8 Embryo showing limb buds.
The Skeleton
becomes subdivided by constrictions into arm, Each bud has a preaxial (or cranial) border and a
forearm and hand. The hand itself soon shows postaxial border (Fig. 10.11). The thumb and great
outlines of the digits. The interdigital areas show toe are formed on the preaxial border.
cell death because of which the digits separate The radius is the preaxial bone of the forearm.
from each other (Fig. 10.9). Similar changes occur In later development, the forelimb is adducted to
in the hindlimb. the side of the body (Fig. 10.11). The original
While the limb buds are growing, the ventral surface forms the anterior surface of the
mesenchymal cells in the buds form cartilaginous arm, forearm and hand. In the case of the lower
models, which subsequently ossify to form the limb, the tibia is the preaxial bone of the leg.
bones of the limb. Adduction of this limb is accompanied by medial
The limb buds are at first directed forward and rotation with the result that the great toe and tibia
laterally from the body of the embryo (Fig. 10.10). come to lie on the medial side. The original ventral
Preaxial border
Forelimb
" bud
Hindlimb
bud
Fig. 10.10 Scheme to show that the longitudinal Fig. 10.11 Scheme showing that with 'adduction' of
axis of the l i m b buds is transverse to the the embryonic limb, the preaxial border
long axis of the embryonic body. becomes the lateral border.
Human Embryology
Cartilage - :•«*;
Dense
Connective tissue connective tissue
of presumptive joint
Loose
connective tissue
Cartilage -
Surroundin_ _
mesenchyme
Capsule
Capsule (^>'^ai;'^JV
» •• •
that the two bones become continuous. This is seen, Supernumerary digits may be present
typically, at the joints between the diaphyses and (Polydactyly). A digit (most commonly the
epiphyses of long bones. thumb) may have an extra phalanx.
The palm or sole may show a deep
At the site where a synovial joint is to be formed, longitudinal cleft {lobster claw).
the mesenchyme is usually seen in three layers. The limbs may remain short in
The two outer layers are continuous with the achondroplasia.
perichondrium covering the cartilaginous ends Sometimes the bone ends forming a joint
of the articulating bones. The middle layer are imperfectly formed (congenital
becomes loose and a cavity is formed in it. The dysplasia). This can lead to congenital
cavity comes to be lined by a mesothelium that dislocation. The hip joint is most
forms the synovial membrane (Fig 10.12). The commonly affected.
capsule, and other ligaments, are derived from
the surrounding mesenchyme.
TIMETABLE OF SOME EVENTS
Anomalies of Limbs MENTIONED IN THIS CHAPTER
1. One or more limbs of the body may be Age Developmental Events
partially, or completely, absent (phoco-
melia, atnelia). These conditions may be 4th week Forelimb bud appears.
produced by ingestion of harmful drugs. (26th day)
2. Parr of a limb may be deformed. Deformi- 4th week Hindlimb bud appears.
ties are most frequently seen in the region (28th day)
of the ankle and foot, and are of various 5th week Limbs become paddle shaped.
types. In the most common variety of 6th week Formation of future digits can be
deformity, the foot shows marked plantar (36th day) seen.
flexion (equinus: like the horse) and Cartilaginous models of bone
inversion (varus). Hence this condition is start forming.
called talipes equinovarus or club foot.
7th week Rotation of limbs occurs.
3. Congenital strictures, congenital ampu-
8th week The elbow and knee are
tations or congenital contractures may be
present. (50th day) established, and fingers and toes
4. There may be abnormal fusion (bony or are free.
fibrous) between different bones of the Primary cenrres of ossification are
limb. Adjoining digits may be fused seen in many bones.
[syndactyly). The phalanges of a digit may 12th week Primary centres of ossification are
be fused to one another (synphalangia). seen in all the long bones.
5. A digit may be abnormally large
{macrodactyly) or abnormally short The extremities are most susceptible to
(brachydactyly). In arachnodactyly, the teratogens during the 4th to 7th weeks; and
fingers are long and thin (spider fingers). slightly less susceptible in the 8th week.
Chapter
Mesenchyme
covering forebrain
Stomatodaeum
Buccopharyngeal
membrane
Foregut
Fig. 11.1 Head end of an embryo just before Fig. 11.2 Formation of frontonasal process.
formation of the frontonasal process. Compare w i t h Fig. 11.1.
foregut (Fig. 9.2B). These are also, therefore, in This arch gives off a bud from its dorsal end. This
very close relationship to the stomatodaeum. It bud is called the maxillary process (Fig. 11.3B). It
will now be readily appreciated that the face is grows ventro-medially cranial to the main part of
derived from the following structures that lie the arch which is now called the mandibular
around the stomatodaeum: process.
The ectoderm overlying the frontonasal process
(a) the frontonasal process; and soon shows bilateral localized thickenings, that
(b) the first pharyngeal (or mandibular) arch are situated a little above the stomatodaeum (Fig.
of each side (Fig. I 1.3A). 11.4A). These are called the nasal placodes. The
formation of these placodes is induced by the
At this stage each mandibular arch forms the underlying forebrain. The placodes soon sink
lateral wall of the stomatodaeum (Fig. 11.3A). below the surface to form nasal pits (Fig. 11.4B).
Frontonasal
process
Stomatodaeum
Mandibular
arch
Frontonasal
process Medial nasal
process
Lens placode Lateral nasal
process
Nasal pit
Eye
\-f~^ Maxillary
j / process
Fig. 11.4 Development of face (continued). (A) The right and left mandibular processes fuse and form the
lower boundary of the future mouth. The nasal placodes appear over the frontonasal process.
The lens placode appears. (B) The nasal placode is converted into the nasal pit. Elevations of the
pit form the medial and lateral nasal processes.
The pits arc continuous with the stomatodaeum nasal process (Fig. 11.5) and then with the
below. The edges of each pit are raised above the medial nasal process (Fig. 11.6). The medial
surface: the medial raised edge is; called the medial and lateral nasal processes also fuse with
nasal process and the lateral edge is called the each other. In this way the nasal pits (now
lateral nasal process. called external nares) arc cut off from the
stomatodaeum.
DEVELOPMENT O F THE FACE The maxillary processes undergo
considerable growth (Fig. 11.6). At the same
We are n o w in a position to study the formation time the frontonasal process becomes much
of the various parts of the face. narrower from side to side, with the result
that the t w o external nares come closer
Lower Lip together.
The mandibular processes of the two sides grow The stomatodaeum is now bounded above
towards each other (Fig. 11.3B) and fuse in the by the upper lip which is derived as follows
midline (Fig. 11.4A). They now form the lower (Figs 11.7, 11.8}.
margin of the stomatodaeum. If it is remembered
(a) The mesodermal basis of the lateral part
that the mouth develops from the stomatodaeum,
of the lip is formed from the maxillary
it will be readily u n d e r s t o o d t h a t the fused
process. The overlying skin is derived
mandibular processes give rise to the lower lip,
from ectoderm covering this process.
and to the lower jaw (Fig. 11.7).
(b) The mesodermal basis of the median
p a r t of the lip (called philtrum) is
Upper Lip
formed from the frontonasal process.
1. E a c h m a x i l l a r y p r o c e s s n o w g r o w s The ectoderm of the maxillary process,
medially and fuses, first with the lateral however, overgrows this mesoderm to
Face, Nose and Palate
Maxillary process
Naso-optic fuses with
furrow Fronto- lateral nasal
nasal process
Primitive mouth
Fused
mandibular proceses
Fig. 11.5 Development of the face (continued). (A) The right and left nasal pits come close to each other.
The lateral nasal process is separated from the maxillary process by the naso-optic furrow.
(B) The maxillary process fuses with the lateral nasal process obliterating the naso-optic furrow.
m e e t t h a t of t h e o p p o s i t e
Frontonasal process m a x i l l a r y p r o c e s s in t h e
midline (Fig. 11.8). As a result,
the skin of the entire upper lip
is innervated by the maxillary
nerves.
Maxillary process 4. The muscles of the face (including
(fused with medial
nasal process) those of the lips) arc derived from
mesoderm of the second branchial
Mandibular process arch and are, therefore, supplied by
the facial nerve.
Frontonasal process
(has become narrow)
Nose
Maxillary and
The nose receives contributions from the
mandibular processes frontonasal process, and from the medial
fuse to form cheek and lateral nasal processes of the right and
Mouth is narrower.
left sides.
We have seen that the external nares
are formed when the nasal pits are cut off
from the stomatodaeum by the fusion of
the maxillary process with the medial
Fig. 11.6 Development of the face (continued). (A) The
nasal process. We have also noted that the
maxillary process extends b e l o w the nasal pit and
external nares gradually approach each
fuses with the medial nasal process. In this way
other. This is a result of the fact that the
the nasal pit is separated from the stomatodaeum.
(B) The maxillary and mandibular processes
frontonasal process becomes progressively
partly fuse to form the cheek. W i t h growth of the narrower and its deeper part ultimately
maxillary processes the nasal pits c o m e closer t o forms the nasal septum. Mesoderm
each other. becomes heaped up in the median plane
Human Embryology
From frontonasal
process"
<W> r\<m> Upper part of cheek
the nose. Simultaneously, a
groove appears between the
from maxillary process regions of the nose and the
From lateral - bulging forebrain (which
nasal process
m a y n o w be c a l l e d t h e
Lower part of cheek
from mandibular process forehead) (Fig. 11.10}. As
the nose becomes prominent,
Lateral part of upper lip the external nares come to
from maxillary process
Median part of open downwards instead of
upper lip from
frontonasal process
forwards (Fig. 11.10). The
Lower lip from
mandibular process external form of the nose is
thus established. The
Fig. 11.7 Derivation of parts of the face. development of the nasal
cavity is considered later.
Lens placode
Maxillary
Nasal /
^ process Eye y0*'
placode /
, Mandibular
o ^ ^ r process
v° J - 1st cleft
7— 2nd arch
A
fK
1st cleft developing
into external ear
B
Fig. 11.9 Early stages in development of the face seen from lateral side.
Face, Nose and Palate
From frontonasal^
\
process-^/
*.*_. j)
/
/
/
process \ \
The development of the eye itself will be dealt From a study of Figs 11.9 and 11.10, it will be
with later (Chapter 19}, bur a brief reference to it seen that when first formed, the pinna lies caudal
is necessary to form a c o m p l e t e idea of the to the developing jaw. It is pushed upwards and
development of the face. backwards to its definitive position due to the
T h e region of the eye is first seen as an great enlargement of the mandibular process.
ectodermal thickening, the lens placode, which If the mandibular process fails to enlarge, the
appears on the ventro-lateral side of the developing ears remain low d o w n . See mandibulofacial
forebrain, lateral and cranial to the nasal placode dysostosis in the following section.
(Fig. 11.4A). The lens placode sinks below the
surface and is eventually cut off from the surface
Developmental Anomalies of the Face
e c t o d e r m . T h e developing eyeball p r o d u c e s a
bulging in this situation (Fig. 11.5). The bulg- It has been seen that the formation of various
ings of the eyes are at first directed laterally parts of the face involves fusion of diverse
(Figs 11.5, 1 1.6} and lie in the angles between the c o m p o n e n t s . T h i s fusion is o c c a s i o n a l l y
maxillary processes and the lateral nasal processes. i n c o m p l e t e a n d gives rise t o v a r i o u s a n o -
With the narrowing of the frontonasal process they malies.
come to face forwards (Figs 11.6, 11.7).
The eyelids are derived from folds of ectoderm 1. Harelip: The upper lip of the hare normally
that are formed above and below the eyes, and by has a cleft. Hence the term harelip is used
mesoderm enclosed within the folds. for defects of the lips.
Human Embryology
ventrally and caudally. There may be The eyes may be. widely separated
presence of cleft palate and of faulty {hypertelorism). The nasal bridge may be
dentition. This condition is called broad. This condition results from the
mandibulofacial dysostosis, Treacher presence of excessive tissue in the
Collins syndrome or first arch syndrome. frontonasal process.
This is a genetic condition inherited as 10. The lips may show congenital pits or
autosomal dominant. fistulae. The lip may be double.
6. One-half of the face may be underdeve-
loped or overdeveloped.
Development of Nasal Cavities
7. The mandible may be small compared to
the rest of the face resulting in a receding The nasal cavities are formed by extension of the
chin {retrognathia). In extreme cases it nasal pits. We have seen that these pits are at first
may even fail to develop (agnathia). in open communication with the stomatodaeum
8. Congenital tumours may be present in (Fig. 11.14A). Soon the medial and lateral nasal
relation to the face. These may represent processes fuse and form a partition between the
attempts at duplication of some parts. pit and the stomatodaeum. This is called the
Pharynx
Stomatodaeum
Fig. 11.14 (A) Parasagittal sections through developing nasal cavity. (A) Nasal pit formed. (B) Nasal pit
deepens. It is separated from the stomatodaeum by the primitive palate. (C) The nasal pit enlarges
to form the nasal sac. Posterior to the primitive palate the sac is separated from the oral cavity by
the bucconasal membrane. (D) Bucconasal membrane breaks d o w n .
Human Embryology
primitive palate (Fig. 11.14B) and is derived from frontonasal process becomes progressively
the frontonasal process. n a r r o w e r . This n a r r o w i n g of the frontonasal
The nasal pits now deepen to form the nasal process, and the enlargement of the nasal cavities
sacs which expand both dorsally and caudally t h e m s e l v e s , b r i n g t h e m closer together. T h e
(Fig. 11.14C). The dorsal part of this sac is, a t intervening tissue becomes much thinned to form
first, separated from the s t o m a t o d a e u m by a the nasal septum (Figs 11.15C, D). The ventral
thin m e m b r a n e called t h e bucconasal mem- part of the nasal septum is attached below to the
brane (or nasal fin). This soon breaks d o w n primitive palate (Fig. 11.15C). M o r e posteriorly,
(Figs 11.14D, 11.15B). The nasal sac now has a ventral the septum is at first attached t o the bucconasal
orifice that opens on the face {anterior or external membrane (Fig. 11.15D), but on disappearance
nares) and a dorsal orifice that opens into the of this membrane it has a free lower edge. The
stomatodaeum {primitive posterior nasal aperture). nasal cavities are separated from the mouth by
The two nasal sacs are at first widely separated the development of the palate.
from one a n o t h e r by the frontonasal process The lateral wall of the nose is derived, on each
(Figs 11.15A, B). We have seen, however, t h a t t h e side, from the lateral nasal process. The nasal
conchae appear as elevations on the
- Frontonasal process - lateral wall of each nasal cavity.
^^^ ^ ^ Nasal sac ^ The original olfactory placodes form
the olfactory epithelium that lies in
\yJ-y- ^ - « Primitive 1 J
the roof, and adjoining parrs of the
walls, of the nasal cavity.
Fig. 11.15 Formation of the nasal septum. (A) and (C) are coronal 2. C o n g e n i t a l defects in t h e
sections through the anterior part of the nasal sac. (B) c r i b r i f o r m p l a t e of t h e
and (D) are sections through the posterior part. (A) Right ethmoid bone may lead to a
and left nasal sacs are widely separated by the frontona- communication between the
sal process. Anterior part of nasal sac is separated from cranial cavity and the nose.
the stomatodaeum by the primitive palate. (B) Posterior 3. The nasal septum may not
part of nasal sac is separated from the stomatodaeum be in the middle line, i.e. it
by the bucconasal membrane. (C) Nasal sacs enlarge may be deflected to one side.
and come close together. The frontonasal process is The septum may be absent.
narrow and forms the nasal septum. The lower edge of
4. T h e n a s a l c a v i t y m a y
the septum reaches the primitive palate. (D) Bucconasal
membrane breaks d o w n . As a result the posterior part
communicate with the
of the nasal sac opens into the stomatodaeum. mouth.
Face, Nose and Palate
Paranasal Sinuses From Figs 11.6 and 11.10, it will be seen that
these processes not only form the upper lip but
The paranasal sinuses appear as diverticula from also e x t e n d b a c k w a r d s on either side of the
the nasal cavity. The diverticula gradually invade s t o m a t o d a e u m . T h e y c a n , t h e r e f o r e , be
the b o n e s after w h i c h they are n a m e d . T h e diagrammatically illustrated as in Fig. 11.16A. If
maxillary and sphenoidal sinuses begin to develop we cut a coronal section through the region (along
before birrh. The other sinuses develop after birth. the line XY in Fig. 11.16A) the maxillary processes
Enlargement of paranasal sinuses is associated will be seen as in Fig. 11.16B. Finally, if we n o w
with overall enlargement of the facial skeleton, c o r r e l a t e Fig. 1 1 . 1 6 B with Fig. 1 1 . 1 5 D t h e
including the jaws. This provides space in the jaws relationship of the maxillary processes to the
for growth and eruption of teeth. Growth of the d e v e l o p i n g nasal cavity a n d m o u t h is easily
facial skeleton is responsible for the gradual change understood (Fig. 11.16C).
in looks of a baby.
From each maxillary process, a plate-like shelf
grows medially (Fig. 11.16D). This is called the
DEVELOPMENT OF THE PALATE palatal process. We now have three components
To understand the development of the palate, let from which the palate will be formed. These are
us have another look at the maxillary process. (Fig. 11.19):
Frontonasal
process
Riqht Maxillary Left
/ process \
0
\!^J Stomatodaeum \ ^ J
0
Vertical section across right and left
Right Maxillary |_eft maxillary processes along
process axis XY shown in Fig. A.
Imaginary horizontal section through
right and left maxillary processes
and the frontonasal process
View similar to (8) after establishment View similar to (C) at a later stage.
of nasal cavity. The nasal septum is Palatal processes grow medially
beginning to form. from each maxillary process.
Median part of the upper lip 1. the two palatal processes; and
2. the p r i m i t i v e p a l a t e f o r m e d from the
frontonasal process.
Premaxilla - Palatal
process The definitive palate is formed by the fusion of
these three parts as follows:
Fig. 11.20 Varieties of cleft palate. (A) Complete non-fusion, giving rise to a Y-shaped cleft, accompanied by
bilateral harelip. (B) The left maxillary process has fused with the premaxilla, but not with the right
maxillary process. The cleft is accompanied by unilateral harelip. (C) Midline cleft extending into
the hard palate. (D) Cleft of soft palate. (E) Bifid uvula.
HIGHLIGHTS
• The oral cavity is derived partly from the
stomatodaeum (ectoderm) and partly from the
foregut (endoderm). These two are separated
by t h e b u c c o p h a r y n g e a l m e m b r a n e t h a t
disappears later (Fig. 12.1).
• Teeth are formed in relation to the dental
lamina (Fig. 12.2). An enlargement of the
lamina is formed for each tooth. It is called
the enamel organ (Fig. 12.6).
• Ameloblasts (derived from ectoderm) form the
enamel. Odontoblasts (derived from mesoderm)
form dentine. T h e pulp is formed by
mesenchyme that invaginates into the enamel
organ (Fig. 12.6E).
• Three swellings a p p e a r in the floor of the
pharynx, in relation to the first pharyngeal
a r c h . These are the right and left lingual
swellings, a n d a m e d i a n swelling the
tuberculum impar (Fig. 12.11). Another median T h e m o u t h is d e r i v e d p a r t l y f r o m t h e
swelling is formed in relation to the third and stomatodaeum and partly from the foregut. Hence
f o u r t h a r c h e s . This is the hypobranchial its epithelial lining is partly ectodermal and partly
eminence. c n d o d e r m a l . A f t e r d i s a p p e a r a n c e of t h e
• The anterior two-third of the tongue is formed buccopharyngeal membrane, the line of junction
from the lingual swellings and the tuberculum between the ectoderm and endoderm is difficult to
impar. define. The epithelium lining the inside of the lips
• The posterior one-third of the tongue is formed by a n d cheeks, a n d the palate, is m o s t probably
the cranial part of the hypobranchial eminence. e c t o d e r m a l . T h e teeth a n d g u m s are also of
• Salivary glands develop as o u t g r o w t h s of ectodermal origin. The epithelium of the tongue
buccal epithelium. is, however, derived from endoderm (Fig. 12.1).
• The palatine tonsil develops in relation to the In the region of the floor of the mouth, the
second pharyngeal pouch. mandibular processes take part in the formation
of three structures. These are:
• The pharynx is derived from the foregut.
Alimentary System I: Mouth, Pharynx and Related Structures
Stomatodaeum-
({ Alveolar process
Buccopharyngeal (teeth and gums)
membrane
- Endoderm—
-Toungue
— Foregut— 1 B
Fig. 12.1 Derivation of the ectodermal part, and endodermal pari of the floor of the mouth.
(A) Stomatodaeum separated from foregut by buccopharyngeal membrane. (B) Buccopharyngeal
membrane disappears. (C) Lips, cheeks and gums lined by ectoderm, tongue by endoderm.
Developing tongue
Linguo-gingival sulcus
Floor of developing mouth
L
Mandibular
process
Labio-gingival sulcus
Up
Alveolar process
Fig. 12.2 (A) The floor of mouth formed by fused mandibular processes. (B) Linguo-gingival sulcus
separates the developing tongue from the rest of mandibular processes. (C) Labio-gingival sulcus
separates alveolar process from lip (or cheek). The dental lamina, seen in the alveolar process,
gives origin to teeth. Also see Fig. 12.3.
A m e l o b l a s t s lay d o w n
enamel on the superficial
_ Maxillary process ( o u t e r ) s u r f a c e of t h e
(Upper lip and cheek) basement m e m b r a n e . T h e
o d o n t o b l a s t s lay d o w n
dentine on its deeper surface.
The process of laying down
of enamel and of dentine is
Labio-gingival furrow similar to that of formation
of bone by osteoblasts. As
layer after layer of enamel
and dentine are laid down,
the layer of ameloblasts and
Arched palate Xj*/f \
the layer of o d o n t o b l a s t s
Labio-gingival furrow move away from each other
Alveolar process
(Fig. 12.7).
After t h e e n a m e l is fully
Fig. 12.4 Development of some structures seen in relation to the formed the ameloblasts
roof of the m o u t h . (A) Maxillary processes and palate. d i s a p p e a r leaving a t h i n
(B) Labio-gingival furrow separates upper lip (or upper m e m b r a n e , the dental
part of cheek) from alveolar process (of upper jaw). cuticle^ over the enamel. The
(C) Medial margin of alveolar process becomes distinct
odontoblasts, however,
because of upward arching of the palate.
c o n t i n u e t o s e p a r a t e the
d e n t i n e from the p u l p
t h r o u g h o u t the life of the
Dental lamina
Enamel organ tooth.
T h e alveolar p a r t s of the
maxillae and mandible are
formed by ossification in the
corresponding alveolar
process. As ossification pro-
gresses, the roots of the teeth
become surrounded by bone.
Dental papilla
Fig. 12.6 Stages in (he formation of a tooth germ. (A) Dental lamina formed by proliferation of ectoderm
lining the alveolar process. (B) Deeper part of dental lamina enlarges to form enamel organ.
(C) Mesodermal cells invaginate the enamel organ to form the papilla. (D) Layer of ameloblasts
(ectoderm) formed from deepest cells of enamel organ. (E) Odontoblasts, derived from
mesodermal cells, form a layer next to the ameloblasts.
Anomalies of Teeth
Dental lamina
1. One or more teeth may be
Outer wall of enamel
organ (disappearing) absent. Complete absence is
called anodentia.
2. Supernumerary teeth may be
present.
3. Individual teeth may be
abnormal. They may be too
large or too small. They may
have supernumerary cusps or
Pulp
roots. Alternatively, cusps or
roots may be less than normal.
4. Two (or more) teeth may be
fused to each other [gemination).
Odontoblasts
5. The alignment of the upper and
lower teeth may be incorrect
(malocclusion). This may be
Part of
caused by one or more of the
developing jaw above anomalies or by defects
of the jaws.
Fig. 12.7 Parts of a developing tooth. Ameloblasts lay d o w n 6. Eruption of teeth may be
enamel. Odontoblasts lay d o w n dentine.
precocious (i.e. too early).
Ossification in relation to mesenchymal cells
surrounding the developing tooth forms the jaw.
Lower incisors may be present
at birth.
Canines 16-20 months 7. Eruption of teeth may be
Second molars 20-39 months delayed. The third molar frequently fails
(b) Permanent Teeth to erupt.
First molar 6-7 years Teeth may form in abnormal situations,
Central incisors 6-8 years e.g. in the ovary or in the hypophysis
Lateral incisors 7-9 years cerebri.
Premolars 10-12 years There may be an improper formation of
Canines 10-12 years the enamel or dentine of the tooth.
Second molars 11-13 years
Third molars 17-21 years TONGUE
Summary of derivation of parts of tooth The tongue develops in relation to the pharyngeal
arches in the floor of the developing mouth. We
Ectoderm Ameloblasts — > - ENAMEL
have seen that each pharyngeal arch arises as a
mesodermal thickening in the lateral wall of the
foregut and that it grows ventrally to become
Mesoderm continuous with the corresponding arch of the
(of neural crest origin ?) Odontoblasts — • DENTINE opposite side (Fig. 12.10). The medial-most parts
of the mandibular arches proliferate to form two
lingual swellings (Fig. 12.11). The lingual
Mesenchyme around tooth CEMENTUM swellings are partially separated from each other
PERIODONTAL LIGAMENT by another swelling that appears in the midline.
Human Embryology
Fifth arch
Tracheal groove
Sixth arch
Lingual swelling
Tuberculum impar
Foramen caecum
. of hypobranchial
eminence
Fourth
arch
The fifth arch
has disappeared
Sixth arch
Mandibular Facial
Epithelium over First arch (Chorda
anterior two-thirds {lingual br.)
tympani)
Occipital
MUSCLE myotomes Hypoglosal
Alimentary System I; Mouth, Pharynx and Related Structures
/ Cloacal
Stomatodaeum " membrane
Proctodaeum
Allantoic diverticulum
Cranially, the foregut is s e p a r a t e d from the to lie outside the abdominal cavity of the embryo.
stomatodaeum by the buccopharyngeal memb- It passes through the umbilical opening into a part
rane. Caudally, the hindgut is separated from the of the extra-embryonic coelom that persists in
proctodaeum by the cloacal membrane. At a later relation to the most proximal part of the umbilical
stage of development, these membranes disappear cord. The loop is subsequently withdrawn into the
and the gut opens to the exterior at its two ends. abdominal cavity.
While the gut is being formed, the circulatory While considering the formation of the allantoic
system of the e m b r y o undergoes considerable diverticulum it was seen that the diverticulum
development. A midline artery, the dorsal aorta, opens into the ventral aspect of the hindgut
is established and comes to lie just dorsal to the (Figs 5.14, 13.1). The part of the hindgut caudal
gut (big. 13.2). It gives off a series of branches ro to the attachmenc of the allantoic diverticulum i*.
the gut. Those in the region of the midgut, initially, called t h e cloaca. T h e cloaca soon s h o w s a
run right up to the yolk sac and are, therefore, subdivision into a broad ventral part and a narrow
called vitelline arteries. Subsequently, most of these dorsal part (Fig. 13.3). These two pans are separated
ventral branches of the dorsal aorta disappear and from each other by the formation of the urorectal
only three of them remain; one for the foregut, septum, which is first formed in the angle between
one for the midgut and one for the hindgut. The the allantois and the cloaca (Figs 13.4A, B). The
artery of the abdominal part of the foregut is the ventral subdivision of the cloaca is now called the
coeliac, that of the midgut is the superior mesenteric primitive urogenital sinus and gives origin to some
and that of the hindgut is the inferior mesenteric. parts of the urogenital system. The dorsal part is
The wide communication between the yolk sac called the primitive rectum. It forms the rectum
and the midgut is gradually n a r r o w e d d o w n and part of the anal canal. The urorectal septum
(Fig. 13.2B> with the result t h a t the m i d g u t g r o w s t o w a r d s the cloacal m e m b r a n e and
becomes tubular. Thereafter, the midgut assumes eventually fuses with it (Fig. 13.4C). The cloacal
the form of a loop (Fig.13.2C). T h e superior membrane is now divided into a ventral urogenital
mesenteric artery now runs in the mesentery of membrane, related to the urogenital sinus, and a
this loop to its apex. The loop can, therefore, be dorsal anal membrane related t o the rectum.
said to have a proximal, or prearterial, segment Mesoderm around the anal membrane becomes
and a distal, orpostarterial, segment. A bud (called heaped up with the result that the anal membrane
caecal bud) soon arises from the postarterial comes to lie at the bottom of a pit called the anal
segment very near the apex of the loop (Fig. 13.2D}. pit, or proctodaeum. The anal pit contributes to
the formation of the anal canal.
For a number of weeks, the midgut loop comes
Human Embryology
Midgut
Prearterial
segment
Superior
mesenteric
artery
Yolk sac_—....-
remnant t—^ f
Vitello-intestinai
duct disappears
Vitelline artery
Abdominal wail
B Yolk sac
Fig. 13.2 Establishment of the midgut loop. (A) Midgut in w i d e c o m m u n i c a t i o n w i t h the yolk sac. Note
vitelline artery passing from dorsal aorta to the yolk sac. (B) Yolk sac m u c h smaller and attached to
midgut through a narrow vitello-intestinai duct. The original vitelline artery gives branches to the
midgut. (Cl The midgut increases in length and forms a l o o p . The l o o p has a prearterial segment
and a postarterial segment. (D) M i d g u t loop passes out of abdominal cavity. The caecal bud arises
from the postarterial segment.
Primitive
rectum
Dorsal part of cloaca Urorectal
septum
A B
Fig. 13.3 Formation of urorectal septum as seen in transverse sections. This septum divides the cloaca into
the primitive urogenital sinus and the primitive rectum.
Alimentary System II: Gastrointestinal Tract
Hindgut
Urogenital membrane
Anal membrane
Fig. 13.4 Formation of urorectal septum as seen in longitudinal sections through the cloaca.
^Ectoderm
~"]0f Intra-embryonic
coelom
|.'.,.|.|.|.|.1.|.'.|.'.|.|..N-l-k.H-.|..|.|.I.M-T
Endoderm
Submucosa,
Notochord Muscle wall, and
Serous layer from
splanchnopleuric
mesoderm
Stomach
Fig. 13.5 Scheme to show h o w the gut is formed
by lateral folding of the embryonic The stomach is first seen as a fusiform dilatation
disc. (A) Embryonic disc before lateral of the foregut, just distal to the oesophagus. Its
folding. (B) The lateral edges of the disc d o r s a l b o r d e r is a t t a c h e d t o t h e p o s t e r i o r
g r o w in a ventral direction. (C) The abdominal wall by a fold of peritoneum called
edges pass medially to meet in the rhe dorsal mesogastrium. Its ventral border is
middle line. In this way, the layer of attached to the septum transversum by another
endoderm is converted into a tube fold of peritoneum called the ventral mesogastrium
w h i c h is the future gut. The ectoderm
(Figs 13.7A, B).
also meets in the m i d l i n e and cuts off
the coelom from the exterior. Subsequently, the liver and the diaphragm are
formed in the substance of the septum transversum.
The ventral mesogastrium now passes from the
stomach to the liver and from the liver to the
DERIVATION OF INDIVIDUAL PARTS d i a p h r a g m and anterior a b d o m i n a l wall (Fig.
OF ALIMENTARY TRACT 13.7C). The part of the ventral mesogastrium
between the liver and the stomach becomes the
Oesophagus lesser omentum, while the part between the liver
T h e oesophagus is developed from rhe part of the and the diaphragm (and anterior abdominal wall)
foregut between the pharynx and the stomach. It gives rise to the coronary and falciform ligaments.
is at first short but elongates with the formation of Similarly, the dorsal mesogastrium is divided
Alimentary System II: Gastrointestinal Tract
Spleen
Liver
Fig. 13.7 (A) Side view of stomach showing the dorsal and ventral mesogastriums.
(B) Transverse section through (A) showing that the ventral mesogastrium
connects the stomach to the septum transversum. (C) The most important
remnant of the ventral mesogastrium is the lesser omentum. It passes from the
stomach to the liver (which develops in the septum transversum). The spleen is
formed in relation to the dorsal mesogastrium. Its formation divides this part of
the dorsal mesogastrium into (he gastrosplenic ligament and the lienorenal
ligament.
by the development of the spleen into a part anterior surface and the original right surface
b e t w e e n s t o m a c h a n d spleen {gastrosplenic becomes the posterior surface.
ligament) and a part between spleen and posterior
abdominal wall called the lienorenal ligament
Duodenum
<Fig. 13.7C).
The stomach undergoes differential g r o w t h The superior (or first) part and the upper half of
resulting in considerable alteration in its shape the descending (or second) part of the duodenum
and orientation. The original ventral border comes are derived from the foregut. The rest of the
to face upward and to the right and becomes the duodenum develops from the most proximal part
lesser curvature. The dorsal border n o w points of the midgut (Fig. 13.8A). T h e part of the gut
downwards and to the left and becomes the greater that gives rise to the d u o d e n u m forms a l o o p
curvature. T h e original left surface becomes its attached t o the posterior abdominal wall by a
Human Embryology
From |
foregut \ ^ / - — - Bile duct _ Dorsal
mesogastrium
B
Mesoduodenum
From
midgut
Fig. 13.8 Development of the duodenum. (A) Part of the duodenum above the entry of
the bile duct is derived from the foregut; and the part below this level is derived
from the midgut. (B) & {Q At first the duodenum has a mesentery called the
mesoduodenum. As seen in (B) this is continuous, cranially, with the dorsal
mesogastrium. The mesoduodenum later disappears (Fig. 13.9).
mesentery (mesoduodenum) (Figs 13.8B, C). Later, In keeping with its development, the proximal
this loop falls to the right. The mesoduodenum part of the duodenum is supplied by branches of
then fuses with the peritoneum of the posterior the coeliac artery and the distal part by branches
abdominal wall, with the result that most of the of the superior mesenteric.
duodenum becomes retroperitoneal (Fig. 13.9). The
mesoduodenum persists in relation t o a small part
of the duodenum adjacent to the pylorus. This is Jejunum and Ileum
the part seen in radiographs as the duodenal cap. The jejunum and most of the ileum are derived
-*- Mesoduodenum
Fig. 13.9 Scheme to show how the mesoduodenum disappears. The duodenum then becomes
retroperitoneal.
Alimentary System II: Gastrointestinal Tract
Artery
midgut loop (Fig. 13.10). The
caecum and appendix are formed
by enlargement of this bud. The
Postarterial proximal part of the bud grows
segment of gut rapidly to form the caecum. Its
distal part remains narrow and
forms the appendix (Fig. 13.11).
During the greater part of fetal
life, the appendix arises from the
apex of the caecum (Fig. 13.11).
Caecal bud -*- Subsequently, the lateral (or right)
wall of the caecum grows much
more rapidly than the medial (or
left) wail with the result that the
Fig. 13.10 Midgut loop. In this figure the loop has been drawn to point of attachment of the
correspond with the orientation of the ileocaecal region in appendix comes to lie on the
postnatal life. (Actually, the prearterial segment is cranial medial side (Fig. 13.11).
to the postarterial segment.)
Descending Colon
The descending colon develops
from the hindgut.
Rectum
The rectum is derived from the
Fig. 13.11 Development of caecum and appendix. The orientation i primitive rectum, i.e. the dorsal
as in Fig. 13.10. subdivision of the cloaca.
Human Embryology
Stomach and
part of duodenum
from foregut
Part of duodenum
(below entry of bile duct)
s*T\ \T n * — V / ^ jejunum and most of
r t \ 1) \ ^ / \ ileum from prearterial
segment of midgut
According to some authorities, the upper part of (Fig. 13.13). The line of junction of the endodermal
the rectum is derived from the hindgut proximal and ectodermal parts is represented by the anal
to the cloaca. valves (pectinate line).
n
- established. It is
lined partly by
Anal endoderm and partly
rtnai
membrane by ectoderm.
membrane
Anal pit lined
by ectoderm M I
Anal valves
Fig. 13.13 (A) Anal membrane separates hindgut from anal pit. (B) Anal membrane disappears. ( Q Scheme
to show the parts of the anal canal in w h i c h the lining epithelium is derived from ectoderm or
endoderm.
Alimentary System If: Gastrointestinal Tract
that persists near the umbilicus. The loop has a important part in establishing the definitive
prearterial (or proximal), segment and a relationships of the various parts of the intestine.
postarterial (or distal), segment (Fig. 13.2C). The steps of the rotation must, therefore, be clearly
Initially, the loop lies in the sagittal plane, its understood.
proximal segment being cranial and ventral to
the distal segment (Fig. 13.14A). The midgut loop Viewed from the ventral side, the loop
now undergoes rotation. This rotation plays a very undergoes an anticlockwise rotation by 90°,
Foregut (stomach)
Midgut loop rotates.
The prearterial segment
comes to lie to the right
and the postarterial
segment to the left.
Right
Postarterial
segment of
midgut (caudal)
Coils of jejunum
and ileum formed
by elongation of
prearterial segment
Coils of jejunum
and ileum pass behind Superior
the artery to the left side. mesenteric artery
As a result the
hindgut (des. colon)
is pushed to the left.
Fig. 13.14 Stages in rotation of the gut. Study these figures carefully along w i t h the corresponding
description in the text. In (E) note that the caecum moves to the right and the transverse c o l o n
now lies in front of the superior mesenteric artery.
Human Embryology
Finally, the p o s t a r t e r i a l
Pre arterial
^^^^^^ segment segment of the midgut loop
/^^\. r e t u r n s t o the a b d o m i n a l
A [> cavity. As it does so, it also
segment
f^i
^r ~ V J J
i Arrows indicate
direction of
(o»Q)° rotates in an anticlockwise
direction (Fig. 13.14E) with
the result the transverse
^^^^^^r rotation.
Artery colon lies a n t e r i o r t o the
superior mesenteric artery
and the caecum conies to lie
Outline of umbilical on the right side. N o t e that
^ ^. opening
all rotation has taken place
iy
{Fig. 13.15).
\
S>
Fig. 13.15 Scheme to show the orientation of the proximal and distal
At this stage the caecum lies
just below the liver, and an
ascending colon cannot be
demarcated. Gradually, the
caecum descends to the iliac
ends of the midgut loop at different phases of the rotation fossa, a n d the ascending,
of the gut. Arrows indicate the direction of rotation. transverse and descending
Compare with Fig. 13.14. parts of the colon become
distinct.
Gall bladder
1A Larynx-^
((I (/I
Fig. 13.20 Annular pancreas surrounding the
duodenum. Trachea- ', I —
m
6. Imperforate anus: This is caused by A B C D
stenosis or atresia or the lower part of the Oesophagus
rectum or the anal canal. Some varieties
of this condition are shown in Figs 13.21 Fig. 13.22 (A) Normal arrangement of trachea and
and 13.23. oesophagus. (B), (C), (D) Various forms of
li,u hro-oesoph.ige.il ristul.ie.
Abnormal Communications or Fistulae
(a) Tracheo-oesophageal fistula: Atresia of the
Parts of the gut may have abnormal oesophagus is often accompanied by
communications with other cavities or with the abnormal communications between the
surface of the body. These are most frequently oesophagus and trachea, as illustrated in
seen in relation to the oesophagus and the Fig. 13.22.
rectum, and are usually associated with atresia (b) Incomplete septation of the cloaca: The
of the normal passage. rectum may communicate with the urinary
Alimentary System II: Gastrointestinal Tract
Sacrum
Pubic
Urinary bladder symphysis \ ^ W
Anal pit
D
J
- \ Anal pit
Abnormal opening
Vagina
Vagina Anal pit
Urethra * /
A n a l pit
Vagina
Fig. 13.23 Various types of rectal fistulae in the male (A to D) and female (E to H). The fistula may be between
rectum and urinary bladder (i.e. recto-vesical) as in (A) and (F), between rectum and urethra
(recto-urethra!) as in (B) and (C), and between rectum and vagina (recto-vaginal) as in (G), (H) and
(F). More than one type may be present at the same time (F). The rectum may open on to the
perineum at an abnormal site (D), (E). In these cases the anal pit is formed at the normal site.
Human Embryology
Fig. 13.24 Degrees of duplication of the gut represented by a cyst on the terminal ileum as in (A), and by
duplication of the entire c o l o n and terminal ileum as in (B).
Duplication
Varying lengths of the intestinal tract may be
duplicated. The duplicate part may form only
a small cyst, or may be of considerable length.
It may or may not communicate with the rest
of the intestine (Fig. 13.24).
Diverticula
These may arise from any part of the gut. They Fig. 13.25 Sites at w h i c h congenital diverticula may
are most common near the duodenum arise from stomach and d u o d e n u m .
(Fig. 13.25).
Persistence of a part of the vitello-intestinal may be present in its wall. (In such cases
duct may give rise to the presence of a ulceration and perforation can occur in the
diverticulum attached to the terminal part of diverticulum.) Occasionally the whole of the
the ileum. This is called Meckel's diverticulum vitello-intestinal duct, or its distal part alone,
or diverticulum ilei. It is of surgical importance may be patent. The former condition leads to a
as it may undergo inflammation giving rise to fecal fistula at the umbilicus. The latter
symptoms similar to those of appendicitis. condition leads to formation of an umbilical
Meckel's diverticulum is also of interest, as sinus. The vitello-intestinal duct may be
pancreatic tissue or a gastric type of mucosa represented by cysts (enterocystoma or vitelline
Alimentary System II: Gastrointestinal Tract
Anterior
abdomial wall
Cyst—1;
Fig. 13.26 Anomalies in relation to the vitello-intestinal duct (See arrows). (A) Meckel's diverticulum.
(B) Patent vitello-intestinal duct. (C) Umbilical sinus. (D) Cyst attached to the abdominal wall. A
cyst may also be seen attached to the gut, or embedded in the abdominal wall as shown in (E).
(E) Stenosis of gut at the site of attachment of duct. (F) Vitello-intestinal duct represented by a
fibrous cord. An umbilical growth arising from remnants of the duct is also shown.
cyst) or by fibrous cords (Fig. 13.26). Fibrous (c) Non-return of umbilical hernia:
cords constitute a danger in later life, as coils Sometimes, the coils of intestine that
of intestine may get twisted round these leading develop from the midgut loop remain
to strangulation. Remnants of the vitello- outside the abdominal cavity. The child is
intestinal duct may also give rise to growths. born with loops of intestine hanging out
of the umbilicus. This condition is called
Errors of Rotation exomphalos or omphalocoele (Fig. 13.28).
(a) Non-rotation ofthe midgut loop: In this Loops of intesrine and other abdominal
condition the small intesrine lies towards contents may also be seen outside the
the right side of the abdominal cavity, and abdominal cavity for an entirely different
the large intestine towards the left reason. In congenital umbilical hernia rhe
(Fig. 13.27A). muscle layer and skin are absent in the
(b) Reversed rotation: The transverse colon region of the umbilicus, creating a defect
crosses behind the superior mesenteric in the abdominal wall through which
artery and the duodenum crosses in front abdominal contents can pass. Such contents
of it (Fig. 13.27B). are covered with peritoneum, but in
Human Embryology
Fig. 13.27 Errors of rotation. (A) Non-rotation. Coils of small intestine lie in the right-half of the abdomen and
colon in the left half. (B) Reversed rotation. The duodenum lies anterior to the superior mesenteric
artery and the colon crosses behind it.
Errors of Fixation
(a) Parts of the intestine that are normally
retroperitoneal may have a mesentery.
Abnormal mobility of this part of the
Umbilical cord
intestine may result in its twisting. This
condition is called volvulus. Twisting of
blood vessels to the loop can lead to
obstruction of its blood supply.
(b) Parts of the intestines, which normally,
have a mesentery, may be fixed by
abnormal adhesions of peritoneum.
Coils of intestine (c) The caecum may remain sub-hepatic or
• Body wall may descend only to the lumbar region.
Alternatively, it may descend into the
pelvis (Fig. 13.29).
Fig. 13.28 Exomphalos. Coils of intestine derived
from the midgut loop fail to return into
Situs Inversus
the abdominal cavity. In this condition all abdominal and thoracic
Alimentary System II: Gastrointestinal Tract
Fig. 13.29 Errors in descent of the caecum. (A) Subhepatic. (B) Lumbar. <C) Pelvic. The normal position is
shown in dotted line in (A) and (B).
viscera are laterally transposed, i.e. all parts and duodenum He on the left side and the
normally on the right side are seen on the left stomach on the right side.
side, and vice versa. For example, the appendix
Foregut — —
Hepatic bud
Ventral
mesogastrium
Midgut
Pars ^^0
_ hepatica ^^m
Gall bladder —
rs cystica I
Fig. 14.1 Development of the biliary apparatus. (A) Hepatic bud arises from the gut at the junction of
foregut and midgut. (B) It grows towards the septum transversum through the ventral
mesogastrium. (C) The bud divides into the pars hepatica (that forms the liver) and the pars cystica
(that forms the gall bladder). The part of the hepatic bud proximal to its division forms the bile
duct.
As the right and left divisions of the pars formation (haemopoiesis). Large aggregations of
hepatica enlarge and extend into the septum blood-forming cells are present between hepatic
transversum, the cells arising from them are cells and blood vessels (Fig. 14.2).
broken up into interlacing columns called hepatic Bile formation begins when the fetus is about
trabeculae. In this process, the umbilical and three months old. The bile is responsible for the
vitelline veins which lie in the septum transversum, black colour of the first stools {meconium) passed
are broken up to form the sinusoids of the liver. by the newborn.
Sinusoids are also formed from the mesenchyme
of the septum transversum.
GALL BLADDER AND BILIARY PASSAGES
The endodermal cells of the hepatic bud give
rise to the parenchyma of the liver and to bile The pars cystica of the hepatic bud gives origin to
capillaries. The mesoderm of the septum the gall bladder and to the cystic duct (Fig. 14.1).
transversum forms the capsule and fibrous tissue The part of the hepatic bud proximal to the pars
basis of the liver. cystica forms the bile duct. The bile duct at first
The fetal liver is an important centre of blood opens on the ventral aspect of the developing
Human Embryology
Hepatic
artery
Portal
triad
Kupffer
vein
eel! Haematopoietic
cells (in fetal life)
duodenum. As a result of differential growth of the uncinate process of the pancreas, while the
the duodenal wall, and as a result of the rotation upper part of the head, the body and the tail are
of the duodenal loop, it comes to open on the formed from the dorsal bud (Fig. 14.6).
dorsomediat aspect of the duodenum along with The duct system of the pancreas is established
the ventral pancreatic bud (Fig. 14.5). as follows. The ducts of the dorsal and ventral
buds anastomose with each other (Fig. 14.7). The
duct of the dorsal bud, between this anastomosis
PANCREAS and the duodenum, remains narrow and forms the
The pancreas develops from two endodermal buds, accessory pancreatic duct {Fig. 14.7C). The main
dorsal and ventral, which arise from the part of pancreatic duct is formed, in its distal part, by the
the gut that later forms the second part of the
duodenum. The ventral bud arises in close relation
to the hepatic bud, in the inferior angle between it
and the duodenum (Fig. 14.3). The dorsal bud
arises from the dorsal aspect of the gut (Figs 14.3,
14.5A) and grows into the mesoduodenum and Hepatic bud
the dorsal mesogastrium. When the duodenal loop
falls to the right, the ventral bud comes to point to
the right and the dorsal bud to the left (Fig. 14.5B). Ventral
pancreatic bud
Thereafter, as a result of differential growth of the
wall of the gut, the attachment of the ventral bud
(along with the bile duct) also shifts to the left
side (Fig. 14.5C). Pancreatic tissue formed from Midgut
these two buds now fuses to form one mass. The
ventral bud forms the lower part of the head and Fig. 14.3 Dorsal and ventral pancreatic buds.
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
,00
- Ventral bud
peritoneum (Fig. 14.8B). The dorsal mesogastrium,
B
1
Fig. 14.5 Changes in relative position of ^
pancreatic buds. (A) Initial position in
w h i c h the ventral and dorsal buds lie in
. J
the direction indicated by their names.
(B) Position after duodenal loop falls to )uct
the right. The ventral b u d n o w points to creatic tissue
the right, and the dorsal bud to the left. From ventral bu J
(C) The attachment of the ventral bud
moves to the left and the t w o buds now Fig. 14.6 Parts of pancreas derived from ventral
lie close together. and dorsal buds.
Human Embryology
Dorsal
mesogastrium - Spleen
Fig. 14.8 Development of the spleen. The spleen appears in the dorsal mesogastrium as in (A) and soon
bulges to the left as in (B).
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
Anomalies of Position
Spleen
(a) The organ may lie trans-
versely on the under-
surface of the right lobe of
the liver, or may lie under
the left lobe (Fig. 14.11G).
(b) The gall bladder may be
lined by peritoneum on all
sides. It may be attached
to the liver by a fold of peri-
toneum or may be comple-
Lienorenal ligament tely free {floating gall
bladder) (Fig. 14.11-1).
(c) It may be embedded in the
substance of the liver
(Fig. 14.11H).
Duplication
(a) The lumen may be,
partially, or completely
subdivided by a septum,
which may, or may not,
extend into the cystic duct
Lesser omentum (Figsl4.HA, B).
(b) The gall bladder may be
Fig. 14.9 Development of the spleen. First see Fig. 14.8. Note the
partially, or completely, dup-
changing relationship of the spleen to the dorsal licated (Figs 14.11B, C).
mesogastrium and to the lesser sac of peritoneum. In (A)
note how part of the dorsal mesogastrium fuses w i t h the Other Anomalies
posterior abdominal w a l l . As a result of this change the
dorsal mesogastrium is divided (at this level) into the
(a) The gall bladder may
gastrosplenic and lienorenal ligaments.
open directly into the bile
duct {sessile bladder)
(Fig. 14.1 IF).
itself, to form a cap-like structure called (b) The gal 1 bladder may be absent
the Phrygian cap (Fig. 14.11D). (Fig. 14.1 OD).
(b) The wall of the infundibulum may project (c) Diverticu la may arise from any part of
downwards as a pouch {Hartmann's the organ
Human Embryology
Ligamentum teres
^ ^ ~ P Porta hepatis _
Inferior vena cava
Fig. 14.10 Anomalies of the liver. (A) Rudimentary left lobe. (B) Anomalous lobation. (C) Reidel's lobe.
(D) Absence of quadrate lobe associated with absence of gall bladder. (E) Accessory liver in
falciform ligament.
Anomalies of the Extrahepatic Duct System right lobe may terminate in the right hepatic
duct, the cystic duct, the bile duct, or even
Abnormal Length
directly into the gall bladder.
There is considerable variation in the level at
which various ducts join each other, with the Anomalies of the Pancreas
result that occasionally some of them
may become abnormally long, or short (a) Annular pancreas: Pancreatic tissue
(Figsl4.12A-D). surrounds the duodenum completely and
may obstruct it (Fig. 13.20).
Abnormal Mode of Termination
(b) Divided pancreas: The parts of the
pancreas derived from the dorsal and
(a) The cystic duct may join the left side of ventral buds fail to fuse with each other
the common hepatic duct, passing either (Fig. 14.15).
in front of it or behind it, to reach its left (c) Accessory pancreatic tissue may be found
side (Figs 14.12E-G). in the stomach, duodenum, jejunum,
(b) The cystic duct may end in the right hepatic Meckel's diverticulum, gal! bladder and
duct (Fig. 14.12H). spleen.
(c) The cystic duct may pass downwards (d) Inversion of pancreatic ducts: The
anterior to the duodenum, before joining embryonic arrangement of the ducts
the common hepatic duct. persists and the greater part of the pancreas
(d) The bile duct may open into the pyloric, is drained through the minor duodenal
or even the cardiac, end of the stomach. papilla (Fig. 14.16).
Ligamentum
S.
- ^ teres
Gall/ £"
Caudate lobe
Right lobe Inferior vena cava
Fig. 14.11 Anomalies of the gall bladder. (A) to (C) Various degrees of subdivision. In (C) there is complete
d u p l i c a t i o n . (D) Phrygian cap. (E) Hartmann's p o u c h . (F) Sessile gall bladder. (Gl Left-sided gall
bladder (1) and transverse gall bladder (2). (H) Gall bladder embedded in liver tissue. (I) Floating
gall bladder, in w h i c h the organ is covered all round by peritoneum.
Human Embryology
D ^
t)
Hepatic ducts missing Bile duct missing Terminal part of
bile duct missing
Fig. 14.13 Agenesis of parts of the extrahepatic biliary tract. Missing parts are indicated in light colour.
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
From dorsal bud 4. The spleen lies on the right side of the
abdomen in situ inversus. The liver and
pancreas are also reversed from side to
side.
LARYNX
Fig. 14.17 Formation of tracheo-bronchial groove. T h e l a r y n x develops f r o m the cranial-most p a r t
o O
Foregut Tracheo-bronchial
groove
Fig. 14.18 Scheme to show how the respiratory diverticulum separates from the foregut. The upper figures
are transverse sections (along the axis XY) of the figures below them. In (C) and (D) note
progressive separation of respiratory diverticulum from the foregut, except at the cranial end.
1 B C
Fig. 14.19 Development of lung buds. (A) Right and left lung buds appear. (B) They divide into lobar bronchi
(3 right, 2 left). (C) Segmental bronchi established.
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
of the respiratory diverticulum. The communi- Within the respiratory passages, some cells
cation between the diverticulum and the pharynx become specialized for production of surfactant.
persists as the inlet of the larynx. The caudal part This substance forms a thin layer over alveoli
of t h e h y p o b r a n c h i a l e m i n e n c e f o r m s t h e and reduces surface tension.
epiglottis. T h e thyroid, cricoid and arytenoid Before birth the respiratory passages are full
cartilages are derivatives of the fourth, fifth and of fluid which also contains surfactant. When
sixth pharyngeal arches. The laryngeal muscles the newborn begins to breathe, the fluid is rapid-
are also derived from branchial mesoderm as ly absorbed and partly expelled. The surfactant
indicated by their nerve supply. remains as a thin layer lining the alveoli. This
prevents collapse of alveoli during expiration.
In premature babies, a deficiency of surfactant
TRACHEA AND BRONCHI may cause difficulty in expansion of the lung
T h e trachea d e v e l o p s from t h e p a r t of t h e and can be a cause of death of the baby.
respiratory diverticulum, that lies between the
point of its bifurcation and the larynx. There is considerable increase in the number
The two primary divisions of the respiratory of alveoli in the postnatal period.
diverticulum form the right and left principal The pulmonary circulation is established early
bronchi. T h e left division comes to lie m o r e in fetal life. However, most of the blood is at first
transversely than the right (Fig. 14.19). It soon short-circuited through the foramen ovale and the
shows two subdivisions that represent the two ductus arteriosus. The amount of blood circulating
lobar bronchi of the left lung. The right division through the lungs progressively increases, and by
divides into three lobar bronchi. the seventh month of intrauterine life the circulation
is rich enough to provide adequate oxygen for
sustaining life. Hence an infant born, thereafter,
LUNGS is viable (i.e. it can live).
T h e substance of the lungs is formed by further T h e d e v e l o p m e n t of the pleural cavities is
subdivisions of the lobar bronchi (Fig. 14.19). (The considered later in this chapter.
total number of divisions of each main bronchus
are about 17 before birth, and six more after birth.) Anomalies of the Larynx
After the establishment of the bronchial tree,
(a) Laryngocoele: In this c o n d i t i o n , t h e
alveoli are formed by expansion of the terminal
laryngeal saccule is abnormally large. It
parts of the tree.
may extend beyond the larynx proper, and
The parts of the lung parenchyma, developing may even form a swelling in the neck.
from the lobar bronchi, are separated from one (b) Congenital stenosis or atresia: There may
another by mesoderm. This mesoderm forms the be stenosis or atresia of the larynx.
connective tissue basis of the lung and also gives (c) The entire larynx, or part of it (e.g. vocal
rise to the pleura. As the pleura lines the surface cords), may be duplicated.
of each lobe separately, the lobes come to be
(d) Laryngoptosis: The larynx lies low down in
separated by fissures.
the neck. Part of it may be behind the sternum.
During the fetal life, all subdivisions of the (e) One or more of the laryngeal cartilages
bronchial tree are lined by a cubical epithelium. may be absent.
This is the canalicular phase of lung development.
With the onset of respiration, after birth, the alveoli Anomalies of the Trachea
b e c o m e d i l a t e d a n d their lining e p i t h e l i u m 1. Tracheo-oesophageal fistulae have already
becomes thin. been described (see Fig. 13.22).
Human Embryology
Tracheal bronchus
Fig. 14.20 Some varieties of tracheal bronchi. (A) Blind bronchus. (B) Supplying accessory lobe.
(C) Replacing apical bronchus.
A complete lung, or one of its lobes (and (a) A transverse fissure may be present
associated bronchi), may fail to develop, or may on the left side with the result that the
left lung has three lobes (Fig. 14.22B).
remain underdeveloped.
(b) The medial basal segment (cardiac
Abnormalities of Lobes lobe) of the left lung may be separated
by a fissure from the rest of the lower
1. Absence of fissures that are normally lobe (Fig. 14.22D).
present: It leads to a reduction in the (c) The superior segment of the lower
number of lobes, e.g. absence of the lobe may be similarly separated
transverse fissure of the right lung results (Fig. 14.22C).
in a right lung with only two lobes (d) A part of the upper lobe of the right
(Fig. 14.22A). lung may come to lie medial to the
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
Fig. 14.22 Abnormal lobes of the lungs: (A) Right lung with only t w o lobes, (B) Left lung w i t h three lobes,
(C) Apical segment of lower lobe is separate. (D) Medial basal segment is separate.
Parietal
" pleura (pink)
Azygos vein
_ Visceral
pleura (black)
Fig. 14.23 Azygos lobe of lung (B). The normal relationship of the azygos vein to the lung is shown in (A).
the aorta. The condition is most frequently of pericardium, pleura and peritoneum are formed
seen in the lower lobe of the left lung. from these layers of mesoderm. The mesodermal
cells lining the cavities differentiate into a flattened
Lung Hernia e p i t h e l i a l l i n i n g c a l l e d rttesothelium. The
mesothelium gives the peritoneum, pleura and
Part of a lung may herniate: (a) through the pericardium their smooth surfaces.
inlet of the thorax, (b) through a defect in the The intra-embryonic coelom is a horseshoe-
thoracic wall, (c) into the mediastinum, or shaped cavity having a narrow midline portion
(d) into the opposite pleural cavity. and two lateral parts. The midline part lies near
the cranial end of the embryonic disc (Fig. 14.25A),
Displaced Bronchi and it is from this part of the coelom that the
These may arise from the trachea above its pericardial cavity is formed. The two lateral limbs
bifurcation or even from the oesophagus. of the coclom form the peritoneal cavity. For some
They may supply: (a) a normal segment of time, the pericardial and peritoneal cavities are
one of the lungs (Fig. 14.20C), (b) an accessory connected t o each other by a pair of n a r r o w
lobe (Figs 14.20B, 14.24), or (c) they may be pericardio-peritoneal canals (Fig. 14.25B). These
blind (Fig. 14.20A). canals undergo great enlargement to form the
pleural cavities.
Details of the development of the pleural and
BODY CAVITIES p e r i t o n e a l cavities a r e c o n s i d e r e d h e r e . T h e
pericardial cavity is considered in Chapter 15.
Introduction
The pericardial, pleural and peritoneal cavities
PLEURAL CAVITY
are derivatives of the intra-embryonic coclom. We
have seen that by the formation of this cavity the After t h e f o r m a t i o n of t h e h e a d f o l d , t h e
lateral plate mesoderm is split into a parietal pericardium comes to lie on the ventral aspect of
(somatopleuric) and a visceral (splanehnopleuric) the embryo, and the pericardio-peritoneal canals
layer (Fig. 5.6). The parietal and visceral layers wind b a c k w a r d s on either side of the foregut
(©)
plate ~~y^y<
A U B
Embryonic^\
Pericardio-
peritoneal canal
Peritoneal cavity
Hindgut
Foregut
Vitello-intestinal duct
Pericardial cavity Septum transversum
Fig. 14.26 Parts of intra-embryonic coelom and their relationship to the gut.
(Fig. 14.26). The lung buds, that arise from the pericardiopleural membranes and the formation
foregut, now invaginate these canals (Fig. 14.27). of the pleuro-peritoneal membranes, respectively
As the buds enlarge to form the kings, the canals (Figs L4.28B,C).
balloon out to form the pleural cavities.
Each pleural cavity now communicates with From Figs 14.28C and 14.29A, it will be seen
the pericardial cavity through the pericardio- that the pleural cavities are at first dorso-lateral
pleural opening, and with the peritoneal cavity to the pericardium. As the lungs increase in
through the pleuro-peritoneal opening size, the pleural cavities extend into the
(Fig. 14.28A). In subsequent development, these mesoderm of the body wall (which is expanding
openings are closed by the formation of the at the same time) and gradually come to He
Foregut Foregut
/~~\ ^ ^ /"V-Pericardio-peritoneal A
B
A Q f T cana, ^Q2
\o
Pericardial Lung bud
cavity
^ ^ ^ Oesophagus
Foregut
*• i
Lung bud
invaginating .
C D
Fig. 14.27 Invagination of pericardio-peritoneal canals by the lung buds.
Human Embryology
Pericardial cavity
Pericardio-peritoneal
canal enlarging to Pericardio-pleural
form pleural cavity membrane
Pleuro-peritoneal
membrane
Peritoneal cavity
A Peritoneal cavity peritoneal
opening
Position of pericardio-
pleural membrane
Pleural cavity
Position of
- pleuro-peritoneal
membrane
Fig. 14.28 Formation of pleural cavity and its separation from pericardial and peritoneal cavities.
(A) Pericardio-peritoneal canal enlarges to form the pleural cavity. The pleural cavity
communicates freely w i t h the pericardial and peritoneal cavities. (B) Pleural cavity is gradually
separated from the pericardial and peritoneal cavities by formation of pericardio-pleural and
pleuro-peritoneal membranes.
lateral, and to some extent ventral, to the membrane. Later this membrane forms the
pericardium (Fig. 14.28B). The pleural cavities fibrous pericardium. This explains the course
also extend downwards into the mesoderm of the phrenic nerve over the pericardium.
forming the posterior abdominal wall, and
upwards towards the neck (Fig. 14.28C). In Fig.
14.29B note that with the expansion of the PERITONEAL CAVITY
pleural cavity the mesoderm of the body wall We have seen that the peritoneal cavity is formed
is split into an outer part that forms the wall of from the two limbs of the horseshoe-shaped intra-
the thorax and an inner part over the pericardial embryonic coelom. The two parts are at first
cavity. The latter is called the pleuro-pericardial separate, but fuse to form one cavity, as a result
membrane. The phrenic nerve runs through this of lateral folding of the embryonic disc
Liver Pancreas, Spleen; Respiratory System; Body Cavities
- Mesoderm of -
body wall
Septum
transversum
Peritoneal _
cavity r
Fig. 14.29 Schemes to show how the pleural cavity expands into the body w a l l .
(Figs 14.30D, E, F). As illustrated in Figs 14.30B, in this membrane. These are the right
C, the two halves of the peritoneal cavity remain and left, pneumato-enteric recesses
separate in the cranial part of the abdomen. (Fig. 14.32B). The left recess soon
The attachment of the mesentery of the primitive disappears. The right recess enlarges and
gut on the posterior abdominal wall is at first in opens into the peritoneal cavity
the midline (Fig. 14.31). As a result of changes (Fig. 14.32C). The cavity of this recess now
involving the rotation of the gut and as a result of enlarges considerably and extends to the
some parts of the gut becoming retroperitoneal, left to form the part of the lesser sac that
the line of attachment of the mesentery becomes lies behind the stomach (Fig. 14.32D). It
complicated (Fig. 14.31). The peritoneal cavity, also extends cranially, on the right side of
therefore, comes to be subdivided into a number the oesophagus and behind the liver
of pockets that are partially separated by folds of (Fig. 14.33). Subsequently, with the
peritoneum. establishment of the diaphragm, the
uppermost part of this cranial extension
Development of Lesser Sac comes to lie above the diaphragm, where
it gives rise to the infracardiac bursa. The
Three distinct processes are involved in the part of the cranial extension that remains
formation of the lesser sac of peritoneum. These below the diaphragm (and behind the
may be considered one by one. liver) forms the superior recess of the lesser
(a) The dorsal mesogastrium that connects the sac.
stomach to the posterior wall of the (b) While the right pneumato-enteric recess
extends to the left, the stomach changes
abdomen is, initially, a thick membrane
its orientation, so that its posterior border
(Fig. 14.32A). Two small cavities appear
Human Embryology
Intra-embryonic
Ectoderm coelom
»( n EEEnnrJEEEEHiB
••IM—
Dorsal
mesogastrium
Ventral
mesogastrium
Fig. 14.30 Schemes to illustrate w h y the foregut has a ventral mesentery (A to C) but the midgut and hindgut
d o not. First refer t o legend t o Fig. 13.5. Figures (A) t o (C) represent the result of lateral f o l d i n g of
the embryonic disc in the region that w i l l form the upper part of the abdomen. As the disc folds
the t w o halves of the intra-embryonic coelom also undergo folding and meet in the middle line
ventral to the gut. From (C) it w i l l be clear h o w the dorsal and ventral mesogastriums are formed.
Figures (D) to (F) show the result of folding in the lower part of the abdomen. In (D) note that, at
this level, each half of the intra-embryonic coelom is open laterally. The result of folding is seen in
(F) from w h i c h it w i l l be clear w h y there is no ventral mesentery here.
(to which the dorsal mesogastrium was the lesser sac. It is continuous with the part
attached}, now faces to the left. This border of the lesser sac lying behind the stomach
forms the greater curvature. The ventral (derived from the right pneumato-enteric
border (to which the ventral mesogastrium recess: N in Fig. 14.34C).
was attached), now comes to face to the (c) With the altered orientation of the stomach,
r i g h t a n d forms t h e lesser c u r v a t u r e the dorsal mesogastrium, which is attached
(Fig. 14.34). The ventral mesogastrium t o t h e g r e a t e r c u r v a t u r e , m a y be
may now be called the lesser omentum. subdivided into t w o parts A and B, as
As a result of this change in the orientation shown in Fig. 14.35. If we trace these two
of the stomach, a part of the peritoneal p a r t s t o the posterior a b d o m i n a l wall
cavity c o m e s t o lie b e h i n d rhe lesser (Fig. 14.35) we find that the attachment
omentum (M in Fig. 14.34C). This part of of the mesogastrium on this wall can also
the peritoneal cavity now forms part of be divided into two corresponding parts.
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
Stomach (
) (
Duodenum U,
Jejunum
and ileum
Ascending
colon
Transverse
colon
Descending
colon
Pelvic colon
Rectum
Fig. 14.31 Peritoneal relations of the gut. In (A) the gut is shown w h e n it is a simple m i d l i n e tube. In (B) the
dorsal w a l l of the abdomen is shown to indicate the m i d l i n e attachment of the dorsal mesentery.
The oesophagus and rectum are seen passing through the w a l l . In (C) it is shown that alternate
segments (3, 5, 7, 9) become retro-peritonea I w h i l e the segments 2, 4, 5 and 8 retain their
mesentery, (D) shows the ultimate disposition of these segments o n the posterior abdominal w a l l .
1 represents the ventral mesogastrium; 2, the dorsal mesogastrium; 3, the d u o d e n u m ; 4 , the
mesentery of the j e j u n u m and i l e u m ; 5, the ascending c o l o n ; 6, the transverse mesocolon; 7, the
descending c o l o n ; 8, the pelvic mesocolon and 9, the rectum.
a
—Dorsal
~"~-
Recess
\ _
y K
mesogastrium extends to
f
opens into •— left behind
Pneumato- -^ peritoneal stomach.
\ enteric ~ cavity.
\ recesses
IV - IL ft
\y ii (( )) 1:1 VI
^Stomach •*"
A B c 0
Fig. 14.32 Development of the lesser sac. Formation of pneumato-enteric recesses.
Part A passes from the stomach to the (Fig. 14.35 ) and forms the greater
spleen as the gastro-splenic ligament, and omentum. The greater omentum undergoes
from the spleen to the left kidney as the enlargement with the result that it comes
lienorenal ligament. It, therefore, forms to increasingly project below the level of
the left margin of the lesser sac. Part B the stomach and becomes folded on itself.
passes from the lower border of the The space within this fold forms the lower
stomach to the posterior abdominal wall part of the lesser sac (Fig. 14.36).
Human Embryology
Right pneumato
- enteric
Fig. 14.33 Development of the lesser sac. Extensions of the right pneumato-enteric recess. Note the
extension above the level of the diaphragm in (C).
Ventral mesogastrium
Stomach
Kidney
mesogastrium Stomach
Fig. 14.34 Schemes to explain formation of the lesser sac. The dorsal and ventral mesogastriums are shown in
(A). Note that the ventral mesogastrium has a free border facing d o w n w a r d s and forwards, if a
section is cut in the plane XY, the appearance seen is illustrated in (B). Subsequently the original
ventral border of the stomach comes to lie on the right side (C). Two parts of the lesser sac labelled
M and N are s h o w n . N is derived from the right pneumato-enteric recess w h i l e M is part of the
peritoneal cavity that comes t o lie behind the ventral mesogastrium {which is now the lesser omentum).
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
PartB
Pyloric end Q
Fig. 14.35 Parts of the dorsal mesogastrium. Part A forms the gastrosplenic and lienorenal ligaments as
shown in Fig. 14.7. Part B elongates to form the greater o m e n t u m . The attachment of these parts
to the stomach is shown in B and to the posterior abdominal w a l l in C.
Fig. 14.36 Development of the lesser sac: D o w n w a r d extension of the sac by elongation and folding of the
greater o m e n t u m . The derivation of the parts numbered in (C) is: (1) f r o m cranial extension of
pneumato-enteric recess; (2) part of peritoneal cavity that comes to lie behind ventral
mesogastrium; (3) right pneumato-enteric recess; (4) cavity produced by elongation and folding of
greater o m e n t u m o n itself.
DIAPHRAGM and pleural cavities are above (or cranial to) it,
whereas the peritoneal cavity is caudal to it. The
Introduction
development of the diaphragm is, therefore,
The diaphragm is a partition that separates the intimately related to the development of these
thoracic and abdominal cavities. The pericardial cavities
Human Embryology
Spinal cord
Dorsal mesentery
of oesophagus
Pleuro-peritoneal
opening
Oesophagus
m transversum
Fig. 14.37 Development of the diaphragm. Pleuro-peritoneal canals and their closure. Note the other
structures in relation to these canals.
The formation of the septum transversum has The diaphragm is, therefore, formed from the
heen considered in Chapter 5. We have seen that following components (Fig. 14.39).
the liver develops in its caudal part. Its cranial
part helps to form the diaphragm. Reference to (a) Septum transversum
Figs 5.12, 5.13 and 5.14 will show that after the (b) Pleuro-peritoneal membranes
establishment of the head fold, the septum (c) Ventral and dorsal mesenteries of
transversum forms a mesodermal mass lying oesophagus
caudal to the pericardial cavity. It, therefore, (d) Mesoderm of body wall, including the
separates the pericardial and peritoneal cavities. mesoderm around the dorsal aorta
Posterior to the septum transversum, however, the
pleural and peritoneal cavities communicate There is, however, considerable controversy as
through the pleuro-peritoneal canals that lie on to how much of the diaphragm is formed from
either side of the oesophagus (Fig. 14.37). The each of the constituents. According to some
partition between the thorax and the abdomen is workers, the septum transversum forms only
completed when the pleuro-peritoneal canals are the central tendon, while according to others it
closed by the formation of the pleuro-peritoneal gives rise to almost the whole of the costal and
membranes (Fig. 14.37). sternal parts of the diaphragm. The crura of
the diaphragm are formed from the mesoderm
of the posterior abdominal wall, as a result of
Development of the Diaphragm the downward extension of the pleural cavities
It may be recalled (Fig. 14.29) that as the pleural into this region (Fig. 14.29).
cavities increase in size, they do so at the expense The nerve supply of the diaphragm from the
of the body wall, with the result that the thorax as third, fourth and fifth cervical nerves (through
a whole also expands. Simultaneously, the the phrenic nerve) shows that the diaphragm
diaphragm has also to enlarge and this enlargement has undergone great migration in a caudal
takes place at the expense of the body wall direction during development. (This descent is
(Fig. 14.38). caused by elongation of the neck, descent of
Liver, Pancreas, Spleen; Respiratory System; Body Cavities
Pleural cavity
Contribution from
body wall
Pleuroperitoneal
membrane
Fig. 14.38 Development of the diaphragm: Schemes to show h o w expansion of the pleural cavities into the
body w a l l causes the w a l l to f o r m part of the d i a p h r a g m .
the heart, and expansion of the pleural cavities.) contents may pass through these gaps to
The sensory innervation of the peripheral parts produce diaphragmatic hernias.
of the diaphragm by the intercostal nerves is Diaphragmatic hernias may be
an evidence of the contribution made by the (Fig. 14.40):
body wall to the muscle.
(a) Posterolateral: due to failure of a
pleuro-peritoneal canal to close.
Anomalies of the Diaphragm
(b) Posterior: due to failure of the
1. Parts of the diaphragm may fail to develop development of the crura.
resulting in gaps in the muscle. Abdominal (c) Retrosternal: due to an abnormally
Pleuro-peritoneal
membrane
Dorsal mesentery &
Ventral mesentery
of oesophagus
Body wall
w
^^^ ^ ^ R Y\ Posterolateral confined to a small area. This condition
is called congenital eventration of the
diaphragm.
Vc-/ ^Wji- central
15 Cardiovascular System
• The renal, suprarenal and gonadal arteries are the main facts are presented first. Details are
formed from lateral splanchnic branches of the presented later.
dorsal aorta.
• Arteries to the body wall and limbs are derived Introduction
from dorsolateral (somatic intersegmental)
branches of the aorta. The heart (like all blood vessels) is mesodermal
in origin. It is formed from splanchnopleuric
• The left subclavian artery is derived from part
of the seventh cervical intersegmental artery. m e s o d e r m lying i m m e d i a t e l y c r a n i a l to the
The right subclavian artery is formed partly prochordal plate. This mesoderm constitutes the
from the seventh cervical intersegmental artery cardiogenic area. It is closely related to the
and partly from the right fourth arch artery. pericardial cavity (which is derived from part of
the i n t r a - e m b r y o n i c c o e l o m ) . For a g o o d
• The portal vein is formed from right and left
understanding of the relationship between the
vitelline veins and anastomoses between them
developing heart tube and the pericardial cavity
(Fig. 15.42).
students are advised to study Figs 5.11 - 5.14.
• The superior vena cava is derived from part of The heart is at first seen in the form of right
the right anterior cardinal vein and from the
and left endothelial heart tubes (Fig. 15.1A) that
right common cardinal vein.
soon fuse with each other. The single tube thus
• The inferior vena cava receives contributions formed shows a series of dilatations. These are:
from several veins (and anastomoses between
them). These are the right posterior cardinal 1. Bulbus cordis
vein, the right s u b c a r d i n a l vein, the right 2. Ventricle (We will refer to it as the primitive
supracardinal vein and the right hepatocardiac ventricle.)
channel. 3. Atrium (We will refer to it as the primitive
atrium or atrial chamber.)
THE HEART 4. Sinus venosus.
Development of the Heart: Main Facts The ventricle and atrium are connected by a
narrow atrio-ventricular canal. The sinus venosus
The development of heart is complex. To avoid has prolongations that are referred to as its right
confusion that may be caused by numerous details, and left horns.
f5^
U Sinus venosus
Fig. 15.1 (A) Right and left heart tubes. (B) to (D) Progressive fusion of tubes from cranial to caudal end.
Fusion of sinus venosus is partial.
Cardiovascular System
Umbilical vein
Fig. 15.2 (A) Arterial end and (B) Venous end of heart tube.
Buibo-ventricular sulcus
Forms primitive left ventricle
(trabeculated part)
Atno-ventncutar
canal
\ Primitive atrium is
f— partitioned to form
right and left atria.
A
(
^r)
^—\y Sinuatrial orifice
v*- S> J -—' c
Septum spurium
/ s Left venous valve
/— N
. (
SL)
x \—, y
Outline of orifice V
X s
) .
Fig. 15.4 Changes in the sinuatrial orifice. Note that firstly, the centrally placed orifice shifts to the right.
Secondly, the orifice that is at first transversely orientated becomes vertical. Dotted lines in (B) and
(C) indicate the outline of the opening in Fig. 15.3 show how the change occurs.
The bulbus cordis lies at the arterial end of the opening. Gradually the opening becomes
heart. It is divisible into three parts, i.e. proximal, narrow and shifts to the right. Finally, it
middle and distal. T h e p r o x i m a l one-third is becomes a n a r r o w slit. The slit has right
dilated and does not have any special name; the and left margins called the right and left
middle one-third is called the conus and the distal venous valves. Cranially, these two valves
o n e - t h i r d is c a l l e d t h e truncus arteriosus fuse to form a structure called the septum
(Figs 15.2A and 15.3). The truncus arteriosus is spurium (Fig. 15.4).
continuous distally with the aortic sac. The aortic
sac is continuous with right and left pharyngeal
arch arteries. These arteries arch backwards to
become continuous with the right and left dorsal
aortae.
A * * c
2. The atrioventricular canal divides into right This blood has t o reach the left atrium,
and left halves as follows (Fig. 15.5). Two and for this p u r p o s e a c o m m u n i c a t i o n
thickenings, the atrio-ventricular cushions between right and left atria is essential.
appear on its dorsal and ventral walls. They Before the septum primum reaches and fuses
grow towards each other and fuse. The fused with the septum intermedium, blood flows
cushions form the septum intermedium through the gap between them. This gap is
(Fig. 15.6). the foramen primum. Before the foramen
primum can be closed it is essential that
Formation of Interatrial Septum another path for flow of blood be created.
This is achieved by breaking d o w n of the
The atrial chamber undergoes division into right
upper part of the septum primum. The new
and left halves by formation of t w o septa (that
gap is the foramen secundum. The septum
later fuse)(Fig. 15.6).
primum now has a free upper edge.
(b) The septum secundum grows down from the
(a) The s^ptam pn'mwrn arises from the roof of
the atrium, to the left of the septum spurium. roof the atrial chamber, to the right of the
It grows d o w n w a r d s t o w a r d s the atrio- septum primum. As it grows it comes to
ventricular canal and ultimately fuses with overlap the free upper edge of the septum
the septum intermedium. primum. Once the two septa overlap, blood
However, note the following carefully. has to flow through the interval between
T h r o u g h o u t fetal life oxygenated blood the septa. This gap is the foramen ovale. It
reaches the right atrium from the placenta. is a valvular aperture that allows blood to
Septum Opening of B
pulmonary vein
im /
Sinuatrial_
orifice
Common atrial
chamber
Foramen secundum
(arrow)
3D
Septum
secundum
Septum primum
(used to A.V.
cushions Right atrium
Fig. 15.6 Formation of interatrial septum. (A) Septum p r i m u m appears. (B) Septum p r i m u m grows towards
fused A.V. cushions. The gap between them is the foramen p r i m u m . ( Q Septum p r i m u m fuses
w i t h A.V. cushions. At the same t i m e the upper part of the septum p r i m u m degenerates to form
the foramen secundum. The septum secundum is formed to the right of the septum p r i m u m .
(D) Septum secundum overlaps the free edge of septum p r i m u m . Blood n o w flows f r o m right to
left through the o b l i q u e cleft between the t w o septa.
Human Embryology
flow from right to left, but not from left to and the venae cavae are seen opening into
right. the atrium.
After birth of the baby the left atrium starts The right margin of the original sinuatrial
receiving oxygenated blood from the lungs orifice (i.e. the right venous valve) expands
and there is no need for flow of blood from very greatly and divides into three parts
right atrium to left atrium. The foramen which form the crista terminalis (Fig. 15.8),
ovale is, therefore, obliterated by fusion of the valve of the inferior vena cava and the
the septum primum and septum secundum. valve of the coronary sinus. N o t e that the
In terms of adult anatomy, the annulus crista terminalis lies at the junction of
ovalis represents the lower free edge of the the part of the right atrium derived from
septum secundum while the fossa ovalis the sinus venosus (sinus venarum) and the
represents the septum primum. atrium proper.
JsC^
common cardinal v.
m e n t of t h e s i n u a t r i a l
orifice (Figs 15.7, 15.8}. R common cardinal v. —
(c) The right half of the atrio-
ventricular canal is also
a b s o r b e d into the right
atrium. Sinuatrial orifice
guarded by right Atrial septum
and left venous
Some relevant facts about the valves
sinus venosus (and its tributaries!
may be noted at this stage. Right atnu
Coronary sinus formed
1. The left horn of the sinus Sinus venosus from L horn of sinus
Terminal part of absorbed into venosus & L common
venosus remains very small. inferior vena cava right atrium cardinal vein
It b e c o m e s p a r t of the from R. vitelline vein
coronary sinus (Fig. 15.7).
2. T h e right common
L venous valve fused
cardinal vein becomes part Superior vena cava with atrial septum
of the superior vena cava. from R common -
cardinal vein
3. T h e right vitelline vein Right venous valve
forms the terminal part of forming crista terminalis
the inferior vena cava.
After absorption of the Right atrium
sinus venosus into the right
atrium the coronary sinus. Fig. 15.7 Incorporation of sinus venosus into the right atrium.
Cardiovascular System
Opening of sinus
venosus into
^L right atrium
Right
venous
valve
V^^Left
^ V venous
W valve
Crista terminalis
Opening of
' coronary sinus
•^ * Valve of
Superior- \ coronary sinus
limbic band inf. limbic band
Opening of inf vena cava Valve of inf. vena cava
Fig. 15.8 Fate of the right and left venous valves. The right venous valve expands greatly and forms the
crista terminalis, the valve of the inferior vena cava and the valve of the coronary sinus. The left
venous valve remains small and fuses with the interatrial septum.
Human Embryology
Important Note
Wall of atrium derived
,» / ., from absorbed vein Please note that in the seventh edition of this
book the bulbus cordis was described as being
s<& ^ ^ ^ ^ % > ^ ^ - L . pulmonary vein divided into t w o parts, i.e. a distal part the
B
C 1 truncus arteriosus, and a proximal part the
L. pulmonary veins conus which was absorbed into the primitive
ventricle, and later formed the smooth outflow
sN>\ parts of both right and left ventricles, it is n o w
X
Truncus Pulmonary trunk Aorta
^ arteriosus
A1
Fused atrio-
ventricular
cushions — Spiral septum
\ Atrium
I 2 1 _ Fused A.v.
Right cushions
atrioventricular /
orifice \ 7 7 \ , Left A.v.
v \ orifice
Common ^ ^ ^ ^ S \
ventricle ^ ! w" x^
Y
A B
Fig. 15.10 (A) Two parts of the ventricular chamber. Part 1 lies anterior to the atrio-ventricular orifice. Part 2
is conical and lies higher up. (B) This is a section across the ventricle in the plane XY, shown in
(A). Sections in the plane indicated by the arrow in (A) are shown in Fig. 15.17.
Cardiovascular System
(a) a dilated lower part (1 in Figure) t h a t 1/3 of bulbus cordis have merged into the primitive
communicates with the atria; and ventricle has to be subdivided into right and left
(b) a conical upper part (2 in Figure) commu- halves in such a way that:
nicating with the truncus arteriosus. Part
' 1 ' is derived from the proximal one-third fa) e a c h half c o m m u n i c a t e s w i t h t h e
of the bulbus cordis a n d the primitive corresponding atrium, and
ventricle, while part ' 2 ' is from the conus. (b) the right ventricle opens into the pulmonary
trunk and the left ventricle into the aorta.
T h e cavity formed after the conus and proximal 1. A septum, called the interventricular septum.
Proliferation from
A.V. cushions Interventricular septum
Trabeculated part
of left ventricle
from primitive
ventricle
Fig. 15.11 Two stages in the formation of the ventricular septum. (B) and (D) correspond to (A) and (C)
respectively. (A) Bulbar septum grows d o w n from above, and interventricular septum grows
upwards from below. (C) and (D) The gap between the bulbar septum and the interventricular
septum is filled in by proliferation from A.V. cushions. For explanation of orientation of these
figures see Legend to Fig. 15.10.
Human Embryology
grows upwards from the floor of the bul no- form small masses of angioblastic tissue. This
ventricular cavity and divides the lower angioblastic tissue gives rise to endothelium and
dilated part of this cavity into right and left also to blood cells. The first blood vessels are
halves (Fig. 15.11A). It meets the fused atrio-
ventricular cushions (septum inter-
medium) and partially fuses with Amniotic cavity
them (Fig. 15.11C). On the external Pericardial cavity in
surface of the heart, the site of cardiogenic area
formation of the interventricular
septum corresponds to the bulbo-
ventricular sulcus (Fig. 15.14A).
2. Two ridges, termed the right and left
bulbar ridges, arise in the wall of the Splanchnopleuric
bulbo-ventricular cavity (in the part mesoderm
derived from the conus). These ridges
grow towards each other and fuse to Foregut
form a bulbar septum (Figs 15.11A,
B). The bulbar septum grows down- Splanchnopleuric
wards towards the interventricular mesoderm
septum but does not quite reach it,
with the result that a gap is left B
between the two.
3. The gap between the upper edge of
the interventricular septum and the
lower edge of the bulbar septum, is
filled by proliferation of tissue from Fused heart tubes
the atrio-ventricular cushions
(Fig. 15.1 ID).
Mesocardium Hole in
mesocardium
Fig. 1 5 . 1 3 Schemes to show the f o l l o w i n g . (A) Heart tube suspended by mesocardium. {Bl Appearance of a
hole in mesocardium. (C) Disappearance of mesocardium resulting in formation of transverse
sinus of pericardium, in Figures (B) to (D) note (1) gradual freeing of heart tube from septum
transversum, and (2) folding of heart tube.
Lower 1 /3
of bulbus
cordis
B
Fig. 15.14 Scheme to show incorporation of conus (and proximal dilated part of bulbus cordis) into the
ventricle by disappearance of the bulbo-ventricular sulcus. Note that the opening of atrium into
ventricle gradually shifts to the centre of the posterior w a l l of the c o m m o n bulbo-ventricular
chamber. The part labelled 'conus' includes the dilated part of the bulbus cordis.
Human Embryology
derived from this e n d o t h e l i u m . T h e vessels heart come to lie dorsal to the pericardial cavity
rapidly proliferate in n u m b e r a n d become and ventral to the foregut (Fig. 5.13).
interconnected to form a vascular system. Soon We have seen that the endothelial heart tube
thereafter, a primitive heart begins to p u m p is derived from the splanchnopleuric mesoderm
blood through this network of vessels with the related to the pericardial cavity (Fig. 15.12A).
result that nutrition from the placenta and yolk After the formation of the head fold, this tube
sac can be m a d e available to the g r o w i n g lies dorsal to the pericardial cavity and ventral
embryo. The heart is, therefore, the first organ to the foregut (Fig. 15.12B). The tube n o w
of the body to start functioning. mvaginates the pericardial sac from the dorsal
We have seen that the pericardial cavity is side. As it d o e s s o , t h e s p l a n c h n o p l e u r i c
formed from the cranial, midline, part of the m e s o d e r m l i n i n g t h e d o r s a l side of t h e
intra-embryonic coelom (Figs 5.6, 5.11). With pericardial cavity proliferates to form a thick
the formation of the coelom, the intra-embryonic layer called the myoepicardial mantle (or
m e s o d e r m of t h e r e g i o n s p l i t s i n t o a epimyocardial mantle) (Figs 15.12C, D). When
somatopleuric layer adjoining the ectoderm (in the invagination is complete, the myoepicardial
the roof of the p e r i c a r d i a l cavity) a n d a mantle completely surrounds the heart tube. It
splanchnopleuric layer adjoining the endoderm gives rise to the cardiac muscle (myocardium)
(Fig. 5.6) a n d f o r m i n g t h e f l o o r of t h e and also to the visceral layer of pericardium
pericardial cavity. The heart develops from (epicardium). The parietal layer of pericardium
angioblastic tissue t h a t arises from this is derived from somatopleuric mesoderm.
s p l a n c h n o p l e u r i c m e s o d e r m , w h i c h is,
therefore, called the cardiogenic area. With the Exterior of the Heart
e s t a b l i s h m e n t of t h e h e a d f o l d , t h e The heart tube is, for some time, suspended
splanchnopleuric mesoderm and the developing from the dorsal wall of the pericardial cavity
Bulbo-ventricular
sulcus
Conus \ / " ~
A l~ venosus
Lower 1/3 of
butbus cordis
by two layers of pericardium that constitute the sinus. Simultaneously, the left horn of the
the dorsal mesocardium (Figs 15.12D, 15.13A). sinus venosus and its tributaries become much
This mesocardium soon disappears and the reduced in size, and the left horn now appears
heart tube lies free within the pericardial sac, to be just another tributary of the right half of
suspended by its two ends (Figs 15.13B, C). the sinus venosus (Fig. 15.16C). Two important
However, at this stage the caudal part of the results of these changes are that:
heart tube (atrium, sinus venosus) is embedded
within the substance of the septum rransversum. (a) The sinuatrial orifice, which was at first
The part of the heart tube lying within the situated in the middle of the posterior
pericardial cavity is thus made up of bulbus aspect of the atrial chamber, now comes
cordis and ventricle. to lie on the right side (Fig. 15.4A - C).
(b) The orifice, which was at first transverse,
This part of the tube g r o w s rapidly and,
now becomes vertical. We have already
therefore, becomes folded on itself to form a
seen t h a t t h e m a r g i n s of t h i s orifice
'LP shaped bulbo-ventricular loop {Fig. 15.13C).
form the right a n d left venous valves
Subsequently, as the atrium and sinus venosus
( F i g s l 5 . 1 6 C , 15.4D).
are freed from the septum transversum, they
come to lie behind and above the ventricle, and
the heart tube is now 'S' shaped (Fig. 15.13D). Some Facts about the Interatrial Septum
At this stage, the bulbus cordis and ventricle N o t e the following additional facts about the
are separated by a deep bulbo-ventricular sulcus formation of the interatrial septum.
(Figs 15.13D, 15.14). This sulcus gradually
becomes s h a l l o w e r so t h a t the c o n u s , the
p r o x i m a l p a r t of t h e b u l b u s c o r d i s a n d ( —\ Atrium
Body of sinus
t h e v e n t r i c l e c o m e t o form o n e c h a m b e r
(Fig. 15.14), which c o m m u n i c a t e s with the
venosus _.
—L_ 1\ ^ Left horn
truncus arteriosus. The atrial chamber which Right horn -.
-><^ /-~N " i ^ Common
:
lies behind the upper part of the ventricle and —\ ( ) (~ cardinal
) /"V 0 \ vein
of the truncus arteriosus, expands; and as it A
\ Umbilical vein
does so parts of it come to project forwards on ^ Vitelline vein
either side of the truncus. As a result of these
changes the exterior of the heart assumes its
definitive shape (Fig. 15.15).
Opening from
atrium to sinus
1
\
)
J Left horn and
venosus \ < ^ „fts tributaries
shifts to right. ) V" retrogress.
Fate of Sinus Venosus
The sinus venosus and the atrial chamber are
at first in open communication with each other
Opening becomes
B 4r*
(Fig. 15.16A). However, they become partially
narrow and is i /
separated by grooves that appear on the lateral guarded by right
wall of the heart tube, at the junction of these and left venous
valves. y? = = ^ - ^ 1 8 now
t w o c h a m b e r s . T h e right g r o o v e r e m a i n s
/ [ Nr a tributary of
shallow but the left one becomes very deep -/ J right horn.
(Figs 15.16B, C) with the result that the left
part of the sinus venosus becomes completely c -\r^i •
separated from the atrial chamber. Its blood Fig. 15.16 Retrogression of the left horn of sinus
now enters the atrium through the right half of
Human-Embryology
T h e lower edge of the septum secundum the septum, rather than by active growth of the
(crista dividens) is chick and firm. In contrast, septum itself.
the upper edge of the septum primum (that forms The membranous part of the interventricular
the lower boundary of the foramen secundum) septum is divisible into an anterior part, which
is thin and mobile like a flap. When blood tends separates the right and left ventricles, and a
to flow from the right to the left atrium, this posterior part which separates the left ventricle
thin flap moves away and there is no obstruction from the r i g h t a t r i u m (also c a l l e d atrio-
to b l o o d flow. H o w e v e r , w h e n t h e r e is a ventricular septum). The anterior part is derived
tendency for blood to flow from left to right from t h e p r o l i f e r a t i o n of tissue from the
this flap comes into apposition with the septum endocardial cushions, as described above. The
secundum and closes the opening. After birth, derivation of the posterior part is shown in
the left atrium begins to receive blood from the Fig. 15.17. It will be seen that the interatrial
lungs and the pressure within this chamber and interventricular septa do not meet the atrio-
becomes greater than that in the right atrium. ventricular cushions in the same line. As a result,
This causes a closure of the foramen ovale, a part of these c u s h i o n s separates the left
which is soon permanently obliterated by fusion ventricle from the right atrium. This part of
of the two flaps. the atrio-ventricular cushions forms the posterior
part of the membranous septum.
Some Additional Facts about the
Interventricular Septum
Valves of the Heart
The interventricular septum is probably formed
more by d o w n w a r d enlargement of the right The mitral and tricuspid valves are formed by
and left ventricular cavities on either side of proliferation of connective tissue under the
Septum secundum
Septum primum
Fused A.V. cushions
(Septum intermedium)
Proliferation from
A.V. cushions joining
Interventricular
septum
Two components that
form the membranous
part of interventricular
septum
Fig. 15.17 In (A) note that the interatrial and interventricular septa d o not meet the atrio-ventricular cushions
in the same plane. In (B) note that the membranous part of the interventricular septum is made up
of (i) the original. A.V. cushion between the attachment of the interatrial and interventricular septa,
and (ii) the endocardial proliferation from these cushions. The first part separates the left ventricle
from the right atrium w h i l e the second part separates the t w o ventricles. The tricuspid valve is
attached to the membranous septum at the junction of these parts. These figures are sections in
the plane indicated by an arrow in Fig. 15.10A.
Cardiovascular System
endocardium of the left and right atrio- After fusion of the two tubes, it lies in the sinus
ventricular canals. venosus. When the sinus venosus is incorporated
The pulmonary and aortic valves are derived into the right atrium, it comes to lie near the
from endocardial cushions that are formed at opening of the superior vena cava.
the junction of the truncus arteriosus and the The atrio-ventricular node and the atrio-
conus (Fig. 15.18A}. Two cushions, right and ventricular bundle form in the left wall of the
left, appear in the wall of the conus. They grow sinus venosus, and in the atrio-ventricular canal.
and fuse with each other (Fig. 15.18B). With After the sinus venosus is absorbed into the right
the separation of the aortic and pulmonary atrium, the atrio-ventricular node comes to lie
openings, the right and left cushions are each near the interatrial septum.
subdivided into two parts, one part going to
each orifice (Fig. 15.18C). Simultaneously, two PERICARDIAL CAVITY
more cushions, anterior and posterior appear.
As a result, the aortic and pulmonary openings We have already noted several important facts
each have three cushions, from which three about the development of the pericardial cavity,
cusps of the corresponding valve develop. and these may be briefly recapitulated as
follows:
The pulmonary valve is at first ventral to
the aortic valve (Fig. 15.18C). Subsequently, 1. The pericardial cavity is a derivative of
there is a rotation so that the pulmonary valve the part of the intra-embryonic coelom that
comes to lie ventral and to the left of the aortic lies in the midline, cranial to the
valve (Fig. 15.18D). It is only after this rotation prochordal plate (Fig. 5.11).
that the cusps acquire their definitive 2. After the formation of the head fold, the
relationships (Pulmonary trunk: one posterior, pericardial cavity comes to lie on the
two anterior; Aorta: one anterior, two posterior). ventral side of the body of the embryo
(Fig. 5.14).
Conducting System of the Heart
3. The heart tube invaginates the
At the stage when there are two heart tubes, a pericardial sac from the dorsal aspect
pacemaker (which later forms the sinoatrial (Figsl5.12C,D).
node) lies in the caudal part of the left tube. 4. The parietal layer of the serous
A B
Posterior
I I <&
Pulmonary
valve
Fig. 15.18 Formation of aortic and pulmonary valves. Note that the vessels undergo an anticlockwise
rotation (compare axis XY in (C) and (D)). It is only after this rotation that the cusps of the aortic
and pulmonary valves acquire their definitive position.
Human Embryology
Venous end
Line of reflection of
' of heart tube
visceral pericardium
- Transverse sinus -
- Truncus arteriosus
E
Sinus venosus
- Transverse sinus -
•<©
Fig. 15.19 Schemes showing the relationship of the heart tube to the pericardial sac. (A), (B) and (C) are
lateral views w h i l e (D), (E), (F) show the dorsal aspect of the interior of the pericardial sac at
corresponding stages. Disappearance of the mesocardium leads to formation of the transverse
sinus of pericardium. Note that with the folding of the heart tube, the arterial and venous ends of
the heart tube are brought closer together, and the transverse sinus comes to lie between them.
Cardiovascular System
are the superior vena cava, inferior vena (b) Ectopia cordis: T h e heart lies exposed, o n
cava and four pulmonary veins (Fig. 15.20A). the front of the chest, and can be seen from
10. The definitive reflections of the pericar- the outside, due to defective development
dium are formed merely by rearrangement of the chest wall.
of these vessels, as shown in Fig. 15.20B.
Rearrangement of the veins at the venous Atresia or Stenosis
end results in the formation of an isolated Any of the orifices of the heart may have too
pouch of pericardium, in relation to the n a r r o w an opening (stenosis), or none at all
four pulmonary veins. This is the oblique (atresia). The aortic and pulmonary passages
sinus of pericardium. may also show supravalvular, or subvalvular,
stenosis (Fig. 15.23). Alternatively, the openings
Congenital Anomalies of the Heart
may be too large as a result of which the valves
Anomalies of Position become incompetent.
In pulmonary stenosis the foramen ovale and
(a) Dextrocardia: The chambers and blood
the ductus arteriosus remain patent. In aortic
vessels of the heart are reversed from side
stenosis also, the ductus arteriosus is patent and
to side, i.e. all structures that normally lie
blood flows into the aorta through it.
on the right side are on the left and vice
versa (Fig. 15.21). This may be a part of
Abnormal G r o w t h
the condition called situs inversus, in which
all o r g a n s a r e t r a n s p o s e d . W h e n There may be accessory cusps in the valves.
dextrocardia is not a part of situs inversus, Congenital tumours may be formed. The left
it is usually accompanied by anomalies a t r i u m m a y be p a r t i a l l y s u b d i v i d e d by a
of the chambers of the heart and of the transverse septum. The myocardium may be
great vessels. poorly developed (hypoplasia).
Pulmonary trunk
Inferior Inferior
vena cava vena cava
Pulmonary veins Parietal pericardium
B
Fig. 15.20 Scheme to show that the oblique sinus of pericardium is established by rearrangement of veins
entering the heart. The sinus is indicated by the lower arrow in (B). The upper arrow indicates the
transverse sinus.
Human Embryology
Aorta -JrT"*>~--^
Pulmonary
£P
^f/(
\
Vv
^v [
/ Superior
vena cava
trunk \/\
Apex ^ • " \ s ^ •> I Inferior Fig. 15,23 Types of aortic stenosis. (A) Valvular.
vena cava (B) Supravalvular. (C) Infravalvular.
Fig. 15.21 Dextrocardia. The chambers and large cushions, as a result of which the fora-
blood vessels show right-left reversal. men primum persists (Fig. 15.24A).
This osteum primum defect can
also be caused by defective formation
of atrio-ventricular endocardial
cushions.
(b) The septum secundum may fail to
develop as a result of which the
foramen secundum remains wide
open [osteum secundum defect;
Fig. 15.24B).
(c) The septum primum and secundum
may develop normally but the oblique
valvular passage between them may
remain patent {patent foramen ovale;
Fig. 15.24C). The patency is signifi-
cant only if there is shunt of blood
Fig. 15.22 Patent truncus arteriosus. The ascending through it. In many cases a probe can
aorta and pulmonary trunk are be passed through the oblique slit
represented by a single channel that (probe patency) but there is no shunt.
opens into both ventricles. (d) Occasionally, there is premature
closure of the foramen ovale (i.e.
before birth). As a result, the right
Defective Formation of Septa
atrium and ventricle undergo great
This results in the formation of abnormal hypertrophy, while the left side of the
passages. heart is underdeveloped.
2. Interventricular septal defects: These may
1. Interatrial septal defects: These may be of
be seen either in the membranous or in
three types.
the muscular part of the septum
(a) The septum primum may fail to reach (Fig. 15.24D). These are the most common
the atrio-ventricular endocardial congenital anomalies of the heart.
Cardiovascular System
Fig. 15.24 Septal defects: (A) Septum primum defect, (B) Septum secundum defect, (C) Patent foramen ovale,
(D) Interventricular septum defect.
-Truncus arteriosus
Fig. 15.26 Relation of first aortic arch to heart tubes. (A) Before fusion of heart tubes. (B) After fusion.
Cardiovascular System
. 7th cervical
intersegmental a.
x
Recurrent laryngeal n.
Branch to lung bud
6th arch
Truncus arteriosus
Fig. 15.28 Fate of aortic arches: (A) Disappearance of 1 st, 2nd and 5th arches.
(B) Disappearance of ductus caroticus o n both sides, and of part of right dorsal
aorta. Part of the right 6th arch also disappears.
Cardiovascular System
Fig. 15.29 (A) The arch of the aorta is derived from (1) the aortic sac, (2) its left horn and (3) the left 4th arch
artery. (B) The descending aorta is derived from (1) the left dorsal aorta and (2) fused dorsal aortae.
(C) The brachiocephalic artery is derived from the right horn of the aortic sac.
left dorsal aorta, below the attachment of (g> As already mentioned, the external carotid
fourth arch artery (1), along with the fused artery arises as a bud from the third arch
median vessel (2) (Fig. 15.29B). artery (Fig. 15.31 A).
(d| The brachiocephalic artery is formed by the (h) The pulmonary arteries are derived from
right horn of the aortic sac (Fig. 15.29C). the part of the sixth arch arteries lying
(e) The proximal part of the right subclavian between the p u l m o n a r y t r u n k and the
artery is derived from the right fourth arch branches t o the lung buds (Fig. 15.31B).
arrery (1), the remaining p;irr of the artery
being derived from the seventh cervical As already stated, the part of the left sixth arch
intersegmental artery (2). On the left side, artery, between the branch to the lung bud and
the subclavian artery is derived entirely the aorta, forms the ductus arteriosus (Fig. 15.31C).
from the seventh cervical intersegmental
artery (3), which arises from the dorsal aorta The relationship of the main nerves of the head
opposite the attachment of the fourth arch and neck to the arteries, can be explained on
artery (Fig. 15.30A). the basis of the development of the arteries.
(f) The common carotid artery is derived, on The nerves of the pharyngeal arches are, at
either side, from part of the third arch first, lateral to the corresponding arteries. T h e
artery, proximal to the external carotid bud nerves of the first, second and third arches (V,
(Fig. 15.30B). The interna! carotid artery is VII & IX) retain their lateral positions. The
formed by the portion of the third arch disappearance of the ductus caroticus, enables
artery distal to the bud (1), along with the the nerve of the fourth arch (superior laryngeal)
original d o r s a l a o r t a c r a n i a l to the to move medially, a n d it comes to lie deep to
a t t a c h m e n t of the third arch artery (2) the main arteries of the neck.
(Fig. 15.30C). T h e nerve of the sixth a r c h ( r e c u r r e n t
As the right third and fourth arch arteries laryngeal), is at first caudal to the artery of
arise from the right horn of the aortic sac, this arch (Fig. 15.32A). With the disappearance
the common carotid and subclavian arteries of part of the sixth arch artery, on the right
become branches of the brachiocephalic side, the nerve moves cranially and comes into
artery. relationship with the right fourth arch artery
Human Embryology
Fig. 15.30 (A) The right subclavian artery is derived (1) from the right 4th arch artery and {2) from the right
7th cervical intersegmental artery. The left subclavian artery is formed only from the left 7th
cervical intersegmental artery. (Bl The c o m m o n carotid artery is derived from the proximal part of
the 3rd arch artery. (C) The internal carotid artery is derived f r o m (1) distal part of the 3rd arch
artery and (2) dorsal aorta (cranial-most part).
Fig. 15.31 (A) The external carotid artery arises as a bud f r o m the 3rd arch artery. (B) The pulmonary arteries
arise from the 6th arch arteries. (C) The ductus arteriosus is derived from part of the left 6th arch
artery.
(subclavian) (Figs 15.32B, C). O n the left side, normal arterial pattern is dependent upon the
it retains its relationship to that part of the sixth disappearance of some parts of the pharyngeal
arch which forms the ductus arteriosus. With arch a r t e r i e s . O c c a s i o n a l l y this process is
the elongation of the neck, and the descent of disturbed in that:
the heart, these nerves are dragged d o w n w a r d s
and, therefore, have to follow a recurrent course 1. Some parts that normally disappear may
back to the larynx. persist; and
2. Some p a r t s t h a t normally persist may
ANOMALOUS DEVELOPMENT OF disappear.
PHARYNGEAL ARCH ARTERIES As a result, several anomalies may be
We have seen t h a t the d e v e l o p m e n t of the produced. Some of these are as follows:
Cardiovascular System
Fig. 15.32 Relationship of the vagus and recurrent laryngeal nerves to the aortic arches. For explanation see
text.
Summary of the adult derivatives of truncus arteriosus, aortic sac and aortic arches
(a) Double aortic arch (Fig. 15.33A).The (d) The right subclavian artery may arise
arterial ring can compress the trachea as the last branch of the aortic arch
and oesophagus. (Fig. 15.33C). Such an artery runs to
(b) Right aortic arch (Fig. 1 5 . 3 3 B ) . the r i g h t b e h i n d t h e o e s o p h a g u s
Normally the aortic arch disappears (Fig. 15.34). Along with the aorta this
on the right side and persists on the artery forms an arterial ring enclosing
left. Reversal of this a r r a n g e m e n t the trachea and oesophagus. The ring
results in a right aortic arch. may press upon a n d obstruct these
(c) T h e ductus arteriosus, w h i c h is tubes. In this abnormality, the right
normally occluded soon after birth, recurrent laryngeal nerve does n o t
may remain patent [patent ductus hook around the subclavian artery. It
arteriosus). passes directly t o the l a r y n x . An
Human Embryology
Fig. 15.35 Anomalies in the pattern of the main branches of the arch of the aorta. (A) Left common carotid
arising from brachiocephalic artery. (B) Left subclavian and left common carotid arising by a
common stem (left brachiocephalic). (C) Left vertebral artery arising directly from arch of aorta.
Human Embryology
Spinal branch
1 Somatic intersegmental
/ branch
^fj Ventral - ^ \
^ \ . division \
/
\r
Ventral splanchnic
branches
Bronchial
Oesophageal
0 Lateral splanchnic
branches
Renal
Coeliac Gonadal
Sup. mesenteric Suprarenal
Inf. mesenteric Phrenic
j \ f \ Ventral division
Fig. 15.37 Sites of vertical anastomoses between branches of dorsal aorta. The fate of the
anastomoses is also shown.
Cardiovascular System
(b) Post-costal, between the costal elements of the seventh cervical intersegmental artery.
and the transverse processes. The main stem of this artery becomes the
(c) Post-transverse, behind the transverse subclavian artery. Like other dorsolateral
processes. arteries, it divides into dorsal, ventral and
lateral divisions. The dorsal division forms the
The pre-costal anastomoses persist as the stem of the vertebral artery (see below). The
thyrocervical trunk, the ascending cervical artery lateral division grows into the upper limb
and the superior intercostal artery. The post- forming the axillary and brachial arteries. The
costal anastomoses form the greater part of the ventral division forms the stem of the internal
vertebral artery. The post-transverse anasto- thoracic (mammary) artery.
moses remain as the deep cervical artery.
The ventral divisions of the somatic Development of the Vertebral Artery
intersegmental arteries are interconnected by (Fig. 15-38)
anastomoses, that are formed on the ventral 1. The first part of the artery, from its origin
aspect of the body wall, near the midline to the point of entry into the foramen
(Fig. 15.39). These form the internal thoracic, transversarium of the sixth cervical
superior epigastric and inferior epigastric vertebra, is formed by the dorsal division
arteries. of the seventh cervical intersegmental
At this stage, special mention must be made artery.
Spinal branch
Somatic
intersegmental.
branches Dorsal div.
Ventral div.
Internal carotid
External carotid
7th cervical
intersegmental artery
4th arch artery
Fig. 15.38 Development of the vertebral artery. In (B) the part labelled 1 is derived from the dorsal division of
the seventh cervical intersegmental artery; 2 from the post-costal anastomoses; and 3 from the
spinal branch of the first cervical intersegmental artery.
Human Embryology
2. The vertical part (second part), lying in to the segments from which the limb buds take
the foramina transversaria, is formed from origin. These vessels form an arterial plexus.
the post-costal anastomoses between the However, each limb soon comes to have one
first to sixth cervical intersegmental axis artery that runs along the central axis of
arteries. the limb. Other arteries, that are formed as
3. The third (horizontal) part, running branches of the axis artery, or as new formations,
transversely on the arch of the atlas, is later take over a considerable part of the arterial
derived from the spina! branch of the first supply as a result of which much of the original
cervical intersegmental artery. axis artery may disappear.
The axis artery of the upper limb is formed
Development of the Internal Thoracic by the seventh cervical intersegmental artery.
Artery (Fig. 15.39) It persists as the axillary, brachial and anterior
interosseous arteries, and as the deep palmar
1. The main stem of the artery is formed by arch. The radial and ulnar arteries appear late
the ventral division of the seventh cervical in development.
intersegmental artery. The left subclavian artery represents the main
2. The vertical part of the artery (including stem of the seventh cervical intersegmental
its superior epigastric branch) is derived artery, and the proximal part of its lateral
from the ventral anastomoses between the division (Fig. 15.39). This explains the origin
ventral divisions of the thoracic inter- of the vertebral (dorsal division) and internal
segmental arteries (intercostal arteries). thoracic (ventral division) arteries from it. The
Development of the Arteries of the Limbs distal part of the right subclavian artery has a
similar origin, but its proximal part is derived,
The limbs are supplied by lateral branches of as already noted, from the right fourth aortic
the somatic intersegmental arteries, that belong arch.
B
Fig. 15.39 Development of the internal thoracic artery.
Cardiovascular System
The axis artery of the lower limb is derived (c) the part of the popliteal artery that lies
from the fifth lumbar intersegmental artery. It above the level of the popliteus muscle,
is seen as a branch of the internal iliac and (d) the distal part of the peroneal artery, and
runs on the dorsal aspect of the limb. The (e) part of the plantar arch.
femoral artery is a new vessel formed on the
ventral aspect of the thigh. Proximally it gets Umbilical Artery
linked above with the external iliac (which is a Before the fusion of the two dorsal aortae, the
branch of the axis artery) and below with the umbilical arteries appear as continuations of
popliteal artery. their distal ends (Fig. 15.40A). After fusion of
In the adult, the original axis artery is the dorsal aortae, they appear as lateral branches
represented by: of the single dorsal aorta (Fig. 15.40B).
Subsequently, each umbilical artery gets linked
(a) the inferior gluteal artery, up with that part of the fifth lumbar
(b) a small artery accompanying the sciatic intersegmental artery which forms the internal
nerve, iliac artery (Fig. 15.40C). The part of the
This part
disappears.
Fig. 15.40 Development of the u m b i l i c a l artery. (A) U m b i l i c a l arteries are seen as continuations o f the right
and left dorsal aortae, before their fusion. (B) After fusion of dorsal aortae, the umbilical arteries
appear as lateral branches of the aorta. They cross the 5th lumbar intersegmental artery (I.S.A.).
(C) U m b i l i c a l arteries establish anastomoses w i t h the 5th lumbar intersegmental artery. (D) The
part of the umbilical artery between the dorsal aorta and the 5th lumbar intersegmental artery
disappears; and the umbilical artery is n o w seen as a branch of the latter. (E) The 5th lumbar
intersegmental artery forms the c o m m o n iliac and internal iliac arteries; and the umbilical is n o w
seen as a branch of the internal iliac.
Human Embryology
Fig. 15.41 U m b i l i c a l and vitelline veins. (A) Note the umbilical and vitelline veins passing through the
septum transversum to reach the sinus venosus. (B) G r o w t h of liver cells w i t h i n the septum trans-
versum breaks up part of the umbilical and vitelline veins into capillaries. Blood reaching the liver
through the umbilical and vitelline veins n o w goes to the heart through the right and left hepato-
cardiac channels. ( Q Left hepatocardiac. channel disappears. (D) Right hepatocardiac channel
(which later forms part of the inferior vena cava) now drains the liver. Right umbilical vein
disappears. All b l o o d from the placenta n o w reaches the liver through the left umbilical vein.
Formation of ductus venosus short circuits this b l o o d to the right hepatocardiac channel.
Cardiovascular System
(a) With the development of the liver, in the septum (c) The right umbilical vein disappears and all
transversum, the proximal parts of the vitelline blood from the placenta n o w reaches the
and umbilical veins become broken up into developing liver through the left vein (N.B.
numerous small channels that contribute to The left vein is 'left') (Fig. 15.41D). In order
the sinusoids of the liver. These sinusoids to facilitate the passage of this blood through
drain into the sinus venosus, through the the liver, some of the sinusoids enlarge to create
persisting terminal parts of the vitelline a direct passage connecting the left umbilical
veins that are n o w called the right and left vein t o the right hepatocardiac channel.
hepatocardiac channels (Fig. 15.41B). The This passage is called the ductus venosus.
proximal parts of the umbilical veins lose (d) While these changes are occurring within
their communications with the sinus venosus. the liver, the parts of the right and left
(b) M e a n w h i l e , t h e left h o r n of the sinus vitelline that lie outside the substance of the
venosus undergoes retrogression and as a liver u n d e r g o alterations leading to the
r e s u l t t h e left h e p a t o c a r d i a c c h a n n e l formation of the portal vein.
disappears. All blood from the umbilical
and vitelline veins now enters the sinus
Development of the Portal Vein
venosus through the right hepatocardiac
channel (also called common hepatic vein). 1. The proximal parts of the two vitelline veins
This vessel later forms the cranial-most part lie o n t h e r i g h t a n d left s i d e s of t h e
of the inferior vena cava (Fig. 15.41C). developing duodenum (Fig. 15.42A).
" Liver
-Vitelline veins
Splenic vein
- Duodenum Superior
mesenteric vein
Splenic and
.*- superior mesenteric
\ ^ veins
Fig. 15.42 Development of the portal vein. (A) Right and left vitelline veins. (B) Vitelline veins joined by three
transverse anastomoses: Cranial ventral, caudal ventral and dorsal. (C) Some of the veins dis-
appear. The portal vein is formed f r o m : 1. Part of left vitelline vein. 2. Dorsal anastomosis. 3. Part
of right vitelline vein. The cranial ventral anastomosis becomes the left branch of the portal vein.
Human Embryology
2. The veins soon become interconnected by three The veins that disappear are:
transverse anastomoses, two of which lie
(a) part of the right vitelline vein caudal to
ventral to the duodenum. The third anastomosis
the dorsal anastomosis;
lies dorsal to the duodenum, and is between
the two ventral anastomoses (Fig. 15.42B). (b) part of the left vitelline vein caudal to the
entry of the superior mesenteric and splenic
3. The superior mesenteric and splenic veins veins;
(which develop independently) join the left
(c) the caudal ventral anastomosis; and
vitelline vein, a short distance caudal to the
(d) the left vitelline vein between dorsal
dorsal anastomosis.
anastomosis and cranial ventral
4. Some parts of the vitelline veins now
anastomosis.
disappear. The portal vein and its right
and left divisions are derived from the veins The veins that persist to form the stem of the
that remain (Fig. 15.42C). portal vein are (Fig. 15.42C):
Subclavian
\
Anterior
cardinal -
Common
cardinal
x
,.' , ' s\
Posterior
cardinal -
B
Anterior, posterior Ant. cardinal v. R. & L anterior Part of anterior
& common cardinal joined by cardinal veins cardinal, common
veins formed subclavian vein joined by an cardinal & posterior
oblique anastomosis cardinal retrogress
on left side
>> A
Fig. 15.43 Fate of anterior cardinal veins, and the development of major veins draining the upper part of the
body.
Cardiovascular System
(a) the left vitelline vein between the entry of 1. the right and left anterior cardinal veins that
the superior mesenteric and splenic veins d r a i n the c r a n i a l p a r t of t h e e m b r y o ,
and the dorsal anastomosis (labelled 1, in including the brain; and
the Figure); 2. the right and left posterior cardinal veins
(b) the dorsal anastomosis itself (2); and that drain the caudal part of the embryo.
(c) the right vitelline vein between the dorsal The anterior and posterior cardinal veins of
anastomosis and the cranial ventral each side join to form the corresponding common
anastomosis (3). cardinal vein (or duct ofCuvier), which open into
the c o r r e s p o n d i n g h o r n s of the sinus venosus
The cranial ventral anastomosis, and a part (Fig. 15.43A).
of t h e left v i t e l l i n e vein c r a n i a l t o t h i s
anastomosis, now form the left branch of the Fate of Anterior Cardinal and
portal vein (4), while the right vitelline vein Common Cardinal Veins
cranial to this anastomosis forms the right
The anterior cardinal veins are joined by the sub-
branch (5). The sinusoids that carry the blood
of t h e s e b r a n c h e s t o the liver s u b s t a n c e clavian veins that drain the forelimbs (Fig. 15.43B).
c o n s t i t u t e t h e venae advehentes. Those Soon thereafter, the anterior cardinal veins become
sinusoids that drain this blood to the inferior i n t e r c o n n e c t e d by a t r a n s v e r s e a n a s t o m o s i s
vena cava are called the venae revehentes and (Fig. 15.43C), proximal to their junction with the
form the tributaries of the hepatic veins. subclavian veins. The part of the left anterior
c a r d i n a l vein c a u d a l t o t h i s a n a s t o m o s i s
The left umbilical vein now ends in the left
retrogresses, and so does the left common cardinal
branch of the portal vein {Fig. 15.42D), while
(Fig. 15.43D).
the ductus venosus connects the left branch of
The Superior Vena Cava (Fig. 15.43F) is derived
the portal vein to the inferior vena cava (right
hepatocardiac channel). from:
(a) the right anterior cardinal vein, caudal to
the transverse anastomosis with the left
Somatic Veins anterior cardinal ( 1 , in the Figure); and
The earliest somatic veins are: (b) the right c o m m o n cardinal vein (2).
Anterior .
cardinal
Body wall -
J 1
Posterior
cardinal -
Fig. 15.44 Formation of the vein for the forelimb b u d . In (A) w e see veins f r o m the body w a l l draining into
the anterior and posterior cardinal veins. In (B) w e see that one of these veins lying at the level of
the limb bud enlarges to drain the l i m b .
Human Embryology
Fig. 15.46 Derivation of the coronary sinus and related structures. 1 and 7 = right and left anterior cardinal
veins; 2 and 8 = posterior cardinal veins; 3 and 6 = c o m m o n cardinal veins; 4 and 5 = right and
left horns of sinus venosus; 9 = right vitelline vein. The fate of these structures is shown in
(B): 1 a and 3a = superior vena cava; 2a = terminal part of the azygos v e i n ; 4a = part of right
a t r i u m ; 5a and proximal half of 6a = coronary sinus; distal half of 6a = oblique vein of left atrium;
7a and 8a = left superior intercostal vein; 9a = inferior vena cava.
Near their caudal ends they receive the Cranially and caudally they communicate
veins of the lower limb bud (external iliac) with the posterior cardinal veins. The
and of the pelvis (internal iliac) subcardinals receive the veins from the
(Fig. 15.47A). The caudal ends of the two developing kidneys.
posterior cardinal veins become inter- At the level of the renal veins, the two
connected by a transverse anastomosis subcardinals become connected by a
(Fig. I5.47B). transverse intersubcardinal anastomosis
The subcardinal veins (green in Fig. 15.47) (Fig. 15.47D). The cranial part of the right
are formed in relation to the mesonephros. subcardinal vein also establishes an
Fig. 15.47 (A) Posterior cardinal veins. (B) Formation of transverse anastomosis. (C) Formation of subcardinal
veins. Note that they drain the developing kidney. (D) The t w o subcardinal veins become
interconnected.
Human Embryology
Fig. 15.48 Development of the inferior vena cava. Subcardinal veins are green, supracardinal veins are
orange, the subcardinal-hepatocardiac anastomosis is yellow, the hepatocardiac channel itself is
purple, and the supracardinal-subcardinal anastomosis is brown. The inferior vena cava receives
contributions from each of these components as indicated by the colour in (D).
Subcardinai
hepatocardiac Inferior vena
anastomosis R. suprarenal v. cava
Left subcardinal
L- suprarenal \
Fig. 15.49 Formation of renal, suprarenal and gonadal veins. The right renal vein is formed as a tributary of
the right subcardinal vein. The left renal vein is derived from (1) vein draining left kidney into left
subcardinal v e i n ; (2) part of left subcardinal vein itself; and (3) inter-subcardinal anastomosis. O n
each side, the suprarenal veins and gonadal veins represent remnants of the subcardinal veins.
From (B) it is seen w h y these veins drain, o n the right side into the inferior vena cava; and on the
left side into the left renal vein.
The left renal vein is derived from: The Azygos System of Veins
(a) the mesonephric vein that originally The veins draining the body wall at first drain
drains into the left subcardinal vein into the posterior cardinal vein (Fig. 15.50A).
(Fig. 15.49A); Their drainage is soon transferred to
(b) a small part of the left subcardinal vein; longitudinal venous channels called the veins
(c) the inter-subcardinal anastomosis. As this of the azygos line (or medial sympathetic line)
anastomosis lies in front of the aorta, the (Fig. 15.50B). Cranially these channels drain
left renal vein has a similar relationship into the posterior cardinal veins. The channels
(Fig. 15.49B). of the two sides are brought into communication
with each other by vessels that run dorsal to
The suprarenal veins are remnants of the part
the aorta (Fig. 15.50B).
of the subcardinal veins above the inter-
subcardinal anastomosis. It is clear from With the retrogression of the left common
Fig. 15.49B that the termination of the right cardinal vein, the left azygos line loses its
suprarenal vein in the inferior vena cava and communication with the posterior cardinal and
that of the left suprarenal vein in the left renal the blood of this channel now drains into the
vein, is because of their developmental origin. right azygos line through the post-aortic
The testicular or ovarian veins are remnants anastomoses. The development of the azygos
of the parts of the subcardinal veins below the system of veins can now be summarized as
inter-subcardinal anastomosis. The reason for follows (Fig. 15.50C).
the difference in the manner of termination of
the veins of the two sides, is obvious from 1. The azygos vein is formed from:
Fig. 15.49B. (a) the vein of the right azygos line; and
Human Embryology
(b) the most cranial part of the right poste- v a r i o u s veins are extremely c o m m o n .
rior cardinal vein through which it Anomalies of major veins are, however, rare.
opens into the superior vena cava (formed Some of these are as follows:
from the right c o m m o n cardinal).
1. Left superior vena cava:This is due to the
2. The vertical parts of the hemiazygos and failure of the left anterior and common
the accessory hemiazygos veins represent c a r d i n a l veins t o r e t r o g r e s s . T h e left
the left azygos line. Their horizontal parts superior vena cava opens into the right
are formed by the post-aortic anastomoses atrium through a large coronary sinus. In
between the azygos lines of the two sides. this condition, the normal (right) superior
3. The second and third left intercostal veins vena cava may be reduced in size or may
r e t a i n t h e i r c o n n e c t i o n w i t h t h e left even be absent (Fig. 15.51).
posterior cardinal vein, and are drained 2. Double inferior vena cava: Generally the
through the left superior intercostal vein. vena cava is double only below the level
4. The abdominal parts of the veins of the of the renal veins (Figs 15.52A - D).
a z y g o s line a r e r e p r e s e n t e d by t h e
(a) Both channels may be present on the
ascending lumbar veins.
right side (Fig. 15.52B). This is caused
by persistence of both the subcardinal
Anomalies of Veins
and supracardinal veins, below the
Minor anomalies in the mode of formation of level of the kidneys.
Fig. 15.50 (A) Veins from the body wall draining into anterior and posterior cardinal veins. (B) With the
formation of the azygos venous channel (Az) most of the veins of the body wall now drain into it.
(C) shows the ultimate arrangement. Note that veins from the 1st intercostal space drain into the
brachiocephalic veins directly (anterior cardinal). The veins of the left 2nd and 3rd spaces drain
into the left superior intercostal vein which is formed partly by the anterior cardinal and partly by
the posterior cardinal veins. On the right side the veins of these spaces drain into the part of the
azygos vein representing the terminal part of the right posterior cardinal.
Cardiovascular System
Right atrium
Coronary sinus
Fig. 15.51 Types of left superior vena cava. The normal pattern is shown in (A).
(b) There may be an additional channel upper part of the inferior vena cava follows
on the left side (Figs 15.52C, D). the course of the azygos vein and opens
into the superior vena cava. The hepatic
Left inferior vena cava: The infrarenal part veins open into the right atrium at the
of the vena cava may be present on the usual site of the inferior vena cava
left side only (Fig. 15.52E). (Figs 15.52F, G).
Azygos continuation of inferior vena cava: Pre-ureteric vena cava: The inferior vena
The hepatic segment of the inferior vena cava normally lies posterior to the right
cava may be absent. This is due to non- ureter. Sometimes it may be anterior to
development of the anastomosis between the right ureter. The ureter then hooks
the right subcardinal vein and the right around the left side of the vena cava. This
hepatocardiac channel. In such cases the anomaly is caused when the infrarenal
Branches from
*— aorta to lower
part of body
Pulmonary
arteries
Inferior A
vena cava m. ^^^^^r
UHl ^^^^ta^M
LIVER Ductus
arteriosus ^^^^B
j^ f c ^ Ductus
'•-•J^L venosus
PLACENTA
\ VjmDiiicai 1
Umbilic i\ arteries
part of the vena cava develops from the (a} oxygenated blood from the right atrium,
subcardinal vein (which lies anterior to and
the ureter} instead of the supracardinal vein (b) a small a m o u n t of deoxygenated blood
(which lies posterior to the ureter}. from the lungs.
4. The pulmonary vessels increase in size and, lymph sacs. Traditionally, these sacs have been
consequently, a much larger volume of considered to be outgrowths from veins.
blood reaches the left atrium from the lungs. However, they are now regarded to be
As a result, the pressure inside the left predominantly independent formations from
atrium is greatly increased. Simultaneously, mesenchyme.
the pressure in the right atrium is diminished Six sacs can be recognized. The right and
because blood from the placenta no longer left jugular sacs lie near the junction of the
reaches it. The net result of these pressure posterior cardinal and subclavian veins (i.e. at
changes is that the pressure in the left the future junction between the internal jugular
atrium now exceeds that in the right atrium and subclavian veins). The right and left
causing the valve of the foramen ovale to posterior (or iliac) sacs lie around the
corresponding common iliac vein. The
retroperitoneal sac (unpaired) lies in relation
The vessels that are occluded soon after birth to the root of the mesentery. The sixth sac (again
are, in due course, replaced by fibrous tissue, and unpaired) is the cisterna chyli. It lies in the
form the following ligaments: midline, some distance caudal to the
retroperitoneal sac.
Vessel Remnant Lymphatic vessels are formed either by
extension from the sacs or may form de novo,
(a) Umbilical arteries Medial umbilical
ligaments and extend into various tissues. Ultimately all
the sacs except the cisterna chyli are invaded
(b) Left umbilical vein Ligamentum teres
by connective tissue and lymphocytes, and are
of the liver
converted into groups of lymph nodes.
(c) Ductus venosus Ligamentum The thoracic duct is derived from right and
venosum left channels that connect the cisterna chyli to
(d) Ductus arteriosus Ligamentum the corresponding jugular sac. The two channels
arteriosum anastomose across the midline. The thoracic
duct is formed from the caudal part of the right
LYMPHATIC SYSTEM channel, the anastomosis between the right and
left channels, and the cranial part of the left
The first signs of the lymphatic system are seen channel. The cranial part of the right channel
in the form of a number of endothelium lined becomes the right lymphatic duct.
Human Embryology
The heart is most susceptible to teratogens between three and six weeks. It can be affected up t
the eighth week.
I
Chapter
16 Urogenital System
Fig. 16.2 Nephrogenic cord (A) and structures that develop in it (B).
CLOACA
RECTUM
1
i \ sinus
Vesicourethral canal Definitive urogenita
I 1 1 i 1 1
URINARY PRIMITIVE PELVIC PHALLIC
BLADDER URETHRA PART PART
Fig. 16.3 Subdivisions of the cloaca. Also see Fig. 16.4.
Urogenital System
important structures are formed in relation to the the primitive urogenital sinus and rectum have been
nephrogenic cord on each side. considered in Chapter 13 (see Figs 13.3 and 13.4).
These are as follows (Fig. 16.2B): In further development, the primitive urogenital
sinus is subdivided into a cranial part, called the
(a) Excretory tubules associated with the vesico-urethral canal, and a caudal part, called
development of the kidney. the definitive urogenital sinus. The openings of
(h) The nephric duct which is formed in relation the mesonephric ducts (see below) lie at the junction
to the developing excretory tubules of these two subdivisions (Fig. 16.4A}. Still later,
mentioned in (a). At later stages, this the definitive urogenital sinus shows a division
becomes the mesonephric duct. into a crania! pelvic part and a caudal phallic
(c) The paramesonephric duct, which is formed part (Fig. 16.4B ).
lateral to the nephric duct. The urogenital system is derived from the
(d) The gonad (testis or ovary), which develops various structures that develop in the intermediate
from the coelomic epithelium lining the mesoderm and from the various subdivisions of
medial side of the nephrogenic cord. the cloaca, as described now.
Cloaca
DEVELOPMENT O F KIDNEYS
The formation of the cloaca and its subdivision into
The definitive human kidney arises from two
distinct sources. The excretory tubules (or
nephrons) are derived from the lowest part of the
nephrogenic cord. This part is the metanephros,
the cells of which form the metanephric blastema.
•- Vesico-urethral canal
Urogenital sinus
_ Urinary bladder
Metanephros
--Primitive urethra
Degenerating
Pronephricduct
duct
Fig. 16.6 Some details of developing
Glomerulus ^ ^ x ^ T ^ pronephros, mesonephros
and metanephros. The
Excretory pronephros and pronephric
mesonephric
tubule duct degenerate soon after
MESONEPHROS formation. The proximal
(Green)
part of the mesonephros
shows segmentation (in
cranio-caudal sequence).
The segments contain
functional excretory tubules
that drain into the
mesonephric duct. Most of
METANEPHROS
these tubules disappear by
the time the metanephros
Ureteric bud
forms the definitive kidney.
Metanephric tissue
/
Ureteric
bud'
#
Major calyx
Minor calyx
Ureteric bud dividing Collecting tubules
into various generations
of branches D
Fig. 16.7 Formation of collecting system of the kidney, from ramifications of the ureteric bud.
Urogenital System
The collecting part of the kidney is derived from through three stages of evolution. The most
a diverticulum called the ureteric bud, which arises primitive of these is called the pronephros. It is
from the lower part of the mesonephric duct the functioning kidney in some cyclostomes and
(Fig. 16.5). fishes. This has been succeeded in higher
vertebrates by the mesonephros, which is the
Some of the features of the development of functioning kidney of most anamniotes. The
kidney in the human embryo can be appreciated kidney of amniotes (including man) is called
only if the evolutionary history of the organ is the metanepbros.
kept in mind. The vertebrate kidney has passed During the development of the human
Metanephric vesicle
Vesicle becomes
pear shaped
Proximal convoluted
tubule
Henle's loop
\J
Fig. 16.8 Scheme to show stages in the development of the nephron.
Human Embryology
Fig. 16.10 Anomalies of the kidney. (A) Congenital polycystic kidney. (B) Aberrant renal arteries. (C) Lobulated
kidney. (D), (E), (F) Transposition of kidney. (G), (HI Horseshoe kidney, and (I) Pancake kidney.
Urogenital System
Mesonephric duct
Mesonephric duct
Part of bladder wall derived
from mesonephric ducts
n
Primitive urethra
Fig. 16.11 (A) Mesonephric duct opens into primitive urogenital sinus. (B) As the sinus grows the proximal
parts of mesonephric clue Is arc absorbed so [hat the mesonephric due is and ureters n o w open
separately- (C) The openings are at first close together. (D) Further absorption of ureters causes
their opening to shift upwards and laterally. The shaded area is derived from absorbed parts of
ureters and mesonephric ducts and is of mesodermal origin. II forms the trigone of the bladder
and the posterior w a l l of part of the urethra.
(c) The kidneys may ascend too far, and (b) Incomplete rotation: T h e hilum is
m a y even be p r e s e n t w i t h i n t h e directed anteromedially.
thoracic cavity. (c) Reverse rotation: The hilum is directed
(d) Both kidneys may lie on one side of anterolaterally.
the midline. They may lie one above
6. Congenital Polycystic Kidney: Failure of
the other or side by side (Figs 16.1 OD,
the excretory tubules of the metanephros
E). The ureter of the displaced kidney
to establish contact with the collecting
crosses to the opposite side across the
tubules, leads to the formation of cysts.
midline.
Isolated cysts are c o m m o n l y seen, but
(e) Both kidneys may be displaced to the sometimes the whole kidney is a mass of
opposite side. The two ureters then such cysts (Fig. 16.10A). The cysts press
c r o s s e a c h o t h e r in t h e m i d l i n e upon normal renal tissue and destroy it.
(Fig. 16.10F).
An a l t e r n a t i v e r e c e n t view on the
5. Abnormal Rotation formation of cysts in the kidney is that
they are derived from a b n o r m a l l y
(a) Non-rotation: The hilun is directed
developed collecting tubules.
forwards.
7. Aberrant Renal Arteries: The kidney may
receive its b l o o d s u p p l y p a r t i a l l y or
e n t i r e l y , f r o m a r t e r i e s a r i s i n g at an
abnormal level (Fig. 16.10B). In the case
of non-ascent, or of incomplete ascent, the
aberrant arteries may constitute the only
supply to the organ. An aberrant artery
may be the only source of arterial blood
t o a segment of the kidney. It may press
upon the ureter and cause obstruction,
leading to hydronephrosis.
8. Multiple Anomalies: Two or more of the
above anomalies may coexist. Anomalies
of position are frequently associated with
those of rotation.
buds now have separate openings into the cloaca DEVELOPMENT OF THE
(Fig. 16.1 IB). These openings are at first close URINARY BLADDER
together (Fig. 16.11C). However, the openings of
the ureteric buds move cranially and laterally due The epithelium of the urinary bladder develops
to continued absorption of the buds. The triangular from the cranial part of the vesico-urethral canal
area (on the dorsal wall of the vesico-urethral (endoderm). The epithelium of the trigone of the
canal) between the openings of the ureteric buds bladder is derived from the absorbed mesonephric
and those of the mesonephric ducts, is derived from ducts (mesoderm). (However, it is later overgrown
the absorbed ducts and is, therefore, of mesodermal by t h e s u r r o u n d i n g e n d o d e r m a l cells.) T h e
origin (Fig. 16.11D). muscular and serous walls of the organ are derived
from splanchnopleuric mesoderm.
DEVELOPMENT OF THE URETER The developing bladder is continuous cranially
with the allantois. It is uncertain whether the
The ureter is derived from the part of the ureteric allantois contributes to the formation of the bladder.
bud that lies between the pelvis of the kidney, and The allantois atrophies and is seen in postnatal
the vesico-urethral canal. life as a fibrous band, the urachus, extending from
the apex of the bladder to the umbilicus.
Anomalies of the Ureter Anomalies of the Urinary Bladder
1. The ureter may be partially or completely 1. T h e urinary bladder may be absent, or
duplicated (Fig. 16.12). This condition may be duplicated.
may, or m a y n o t , be a s s o c i a t e d with
2. The sphincter vesicae may be absent.
duplication of the kidney. Very rarely, there
3. The lumen of the urinary bladder may be
may be more than t w o ureters on one, or
divided into compartments by septa.
both sides. Of the two ureters one may
4. The bladder may be divided into upper
open into the urinary bladder while the
and lower c o m p a r t m e n t s (hourglass
other may open at an abnormal site (see
bladder) because of a constriction in the
below).
middle of the organ (Fig. 16.14A).
2. Instead of opening into the urinary bladder, 5. The bladder may communicate with the
the ureter may end in the prostatic urethra, rectum (Figs 13.25A, H ) .
ductus deferens, seminal vesicles or rectum,
in the male (Fig. 16.13B); a n d in the
urethra, vagina, vestibule or rectum in the
female (Fig. 16.13A).
3. The upper end of the ureter may be blind,
i.e. it is not connected to the kidney.
4. The ureter may be dilated {hydroureter)
because of obstruction to urine flow.
5. The ureter may have valves or diverticula.
6. T h e right ureter may pass behind the
inferior vena cava. It then hooks around
the left side of the vena cava; this may
result in kinking and obstruction of the
Fig. 16.14 Anomalies of the bladder. {A) Hourglass
ureter. The real defect is in the develop-
bladder. (B) Ectopia vesicae. The ureteric
ment of the vena cava as described in
Openings and the trigone are seen o n the
Chapter 15.
surface of the body.
Urogenital System
"emale urethra
Prostatic urethra
Membranous urethra
oo
Fig. 16.15 Development of urethra. (A) Primitive UGS showing opening of
mesonephric ducts. (B) Primitive UGS divided into vesico-
urethral canal and definitive UGS. Mesonephric ducts and
ureters open separately at the junction of the t w o parts.
( O Vesico-urethral canal subdivided into urinary bladder and
primitive urethra. The definitive UGS divides into pelvic and
phallic parts. (D) The female urethra is formed from the primitive
urethra and from part of the pelvic portion of UGS. The rest of
the pelvic part of UGS forms the vestibule. (E] In the male the
prostatic urethra is formed in the same w a y as the female
urethra. The membranous urethra is derived from the pelvic part
of UGS. The penile urethra is derived from the phallic part of
UGS. Red circles = openings of mesonephric ducts and ureters.
Blue = part derived from mesoderm. Green = ectoderm.
Human Embryology
6. Ectopia vesicae: The lower part of the from the mesonephric ducts and is, therefore,
anterior abdominal wall, as well as the mesodermal in origin. The female urethra may
v e n t r a l w a l l of t h e b l a d d e r , m a y be receive a slight contribution from the pelvic part
missing. As a result, the cavity of the of the urogenital sinus (Fig. 16.15).
bladder may be exposed on the surface of
the b o d y (Fig. 16.14B). This defect is
DEVELOPMENT OF THE
usually associated with epispadias. Ectopia
MALE URETHRA
vesicae is caused by failure of mesoderm
to migrate into the lower abdominal wall (a) The part of the male urethra extending from
(between umbilicus and genital tubercle). the urinary bladder up to the openings of
F a i l u r e of m i g r a t i o n m a y be d u e t o the ejaculatory ducts (original openings of
excessive d e v e l o p m e n t of the cloacal mesonephric ducts), is derived from the
membrane. The ectoderm of the anterior caudal part of the vesico-urethral canal
abdominal wall and the endoderm of the (endoderm). The posterior wall of this part
ventral wall of the urinary bladder remain is derived from the absorbed mesonephric
unsupported and thin. Their rupture leads d u c t s ( m e s o d e r m ) . (It m a y l a t e r b e
to the exposure of the cavity of the urinary overgrown by endoderm.)
bladder. (b) The rest of the prostatic urethra, and the
7. Congenital diverticula may be present. membranous urethra, are derived from the
These are found at the junction of the pelvic p a r t of the definitive u r o g e n i t a l
trigone with the rest of the bladder. sinus.
(c) The penile part of the urethra (except the
DEVELOPMENT OF THE terminal part) is derived from the epithelium
FEMALE URETHRA of the phallic part of the definitive urogeni-
tal sinus (see 'Development of Penis').
The female urethra is derived from the caudal part (d) The terminal part of the penile urethra, that
of the vesico-urethral canal (endoderm). We have lies in the glans, is derived from ectoderm
seen that the posterior wall of this canal is derived (Fig. 16.15).
Capsule
Stroma (muscle,
connective tissue)
Prostatic utricle
Glands opening onto
posterior wall of urethra
above ejaculatory ducts
Fig. 16.16 Mesodermal and endodermal derivatives of the prostate. The glands of the median lobe, w h i c h
open onto the posterior wall of the prostatic urethra (above the opening of the ejaculatory ducts)
are mesodermal. Figure (A) shows a transverse section above the level of the opening of
ejaculatory ducts. Figure (B) is a sagittal section.
Urogenital System
Gonad
uI- "1/
w
% • - « - Mesonephnc -*-mm
1 Paramesonephric mm
w
^M duct mm
\
Utero-
vaginal
canal
A B
Fig. 16.18 Formation of utero-vaginal canal by fusion of the caudal parts of paramesonephric ducts.
Human Embryology
hc:\ rgN
>// Prostatic
! utricle
r l 2
X Appendix of
3 V
testis
fpJLry.
A
0
/*C
B
Testis
Fig. 16.19 Fate of paramesonephric ducts. (A) In the female they form the uterine tubes, the uterus and part
of the vagina. (B) In the male most of the duct disappears. Remnants are seen as the appendix of
the testis and the prostatic utricle.
The secretory elements of the prostate are from the urogenital sinus form the paraurethral
rudimentary at birth. They undergo consi- glands of Skene.
derable development at puberty. The organ
undergoes progressive atrophy in old age, but PARAMESONEPHRIC DUCTS
in some men it undergoes benign hypertrophy.
The prostate may, rarely, be absent. We have seen that these ducts are present in the
intermediate mesoderm. They are formed by
Female Homologues of Prostate invagination of coelomic epithelium (Fig. 16.17).
They lie lateral to the mesonephric ducts in the
Endodermal buds, similar to those that form cranial part of the nephrogenic cord (Fig. 16.18A).
the prostate in the male, are also seen in the When traced caudally they cross to the medial
female. The buds that arise from the caudal side of the mesonephric ducts. Here the ducts of
part of the vesico-urethral canal give rise to the two sides meet and fuse in the middle line to
the urethral glands^ whereas the buds arising form the utero-vaginal canal (or uterine canal)
Fig. 16.20 Anomalies of the uterus. (A) Duplication of uterus and vagina. (B) Bicornuate uterus. (C) Septum in
uterus. (D) Unicornuate uterus.
Urogenital System
(Fig. 16.18B). The caudal end of this canal comes Anomalies of the Uterus
in contact with the dorsal wall of, the definitive
urogenital sinus. We have already seen that, in 1. The uterus may be completely, or partially,
the female, this part of the sinus give rise to the duplicated (Figs 16.20A, B). Complete
vestibule. In the female, the paramesonephric ducts duplication is referred to as uterus
give origin to the uterine tubes, the uterus and didelphys.
part of the vagina (Fig. 16.19A). 2. The lumen may be partially, or completely,
subdivided by a septum (Fig. 16.20C).
3. The entire uterus may be absent.
DEVELOPMENT OF UTERUS AND
4. One half of the uterus may be absent
UTERINE TUBES {unicornuate uterus) (Fig. 16.20D).
The epithelium of the uterus develops from the 5. The uterus may remain rudimentary.
fused paramesonephric ducts (utero-vaginal canal: 6. There may be atresia of the lumen either
1 in Fig. 16.19A). The myometrium is derived in the body or in the cervix.
from surrounding mesoderm (3). As the thickness
Anomalies of the Uterine Tubes
of the myometrium increases, the unfused
horizontal parts of the two paramesonephric ducts 1. The uterine tubes may be absent, on one
come to be partially embedded within its or both sides.
substance, and help to form the fundus of the 2. The tubes may be partially, or completely,
uterus (2). The cervix can soon be recognized as a duplicated on one or both sides.
separate region. In the fetus the cervical part is 3. There may be atresia of the tubes.
larger than the body of the uterus.
The uterine tubes develop from the unfused parts DEVELOPMENT OF VAGINA
of the paramesonephric ducts. The original points
of invagination of the ducts into the coelomic We have noted that the lower end of the utero-
epithelium remain as the abdominal openings of vaginal canal comes in close contact with the
the tubes. Fimbria are formed in this situation. dorsal wall of part of the urogenital sinus
Sinovaginal
Utero-vaginal canal bu|b
/ V
Fig. 16.21 (A) Utero-vaginal canal (mesoderm) in contact with lining of UGS (endoderm). (B) Sinovaginal
bulbs are formed by proliferation of endodermal lining. (C) Solid vaginal plate derived partly from
mesoderm of utero-vaginal canal and partly from endoderm of sinovaginal bulbs. (D) Vagina
formed by canalization of vaginal plate.
Human Embryology
Genital
tubercle
Urogenital
membrane
Cloacal _
membrane • _\ n / "O Genital
swelling
r\
• c
Urogenital
membrane
V
swelling [ I V I / \ -_/'
Openinq into S* —
Urogenital sinus Vestibule —Anus
Fig. 16.23 (A) Cloacal membrane. (B) Cloacal membrane divides into urogenital membrane and anal
membrane. (C) Right and left genital swellings, and a median genital tubercle appear.
(D) Urogenital membrane breaks d o w n . Its edges form the primitive urethral folds.
(E) Genital tubercle becomes the clitoris. The genital swellings become the labia majora,
and the primitive urethral folds become the labia minora.
Urogenital System
Phallic part of
urogenital sinus
Solid ectodermal
Q downgrowth
Raphe
Raphe Scrotum
Human Embryology
Open groove
under penis Various levels
at which urethra
Half of scrotum may open
Urethral opening
Fig. 16.27 (A) Cleft scrotum. (B) Hypospadias. The urethra opens onto the ventral aspect of the penis.
Urogenital System
endodermal cells, is now formed on the prepuce, may be missing. The opening of
undersurface of the phallus (Fig. 16.26F). the prepuce may be too narrow to allow
At the base of the phallus this groove is retraction (phimosis).
continuous with the cavity of the urogenital 2. The penis may be double or bifid.
sinus (Fig. 16.26F). The margins of this 3. Rarely, the penis may lie posterior to the
groove are called the definitive urethral scrotum.
folds. 4. The urethral folds may fail to fuse,
These folds now approach and fuse with partially, or completely. When failure to
each other. The fusion begins posteriorly fuse is complete the scrotum is in two
in the region of the urogenital sinus and halves and the genitals look like those of
extends forwards onto the phallus the female (Fig. 16.27A). If the defect is
(Figs 16.26G, H). The penile urethra is confined to the anterior part of the phallus,
formed as a result of this fusion. It will the urethra opens on the undersurface of
now be apparent that the wall of the penile the penis. This condition is called
urethra is made up of: hypospadias (Fig. 16.27B).
5. The urethra sometimes opens on the dorsal
(i) the original endodermal lining of the
aspect of the penis. The condition is called
phallic part of the urogenital sinus, and
epispadias, and is usually associated with
(ii) the endodermal cells of the urethral
ectopia vesicae. In such cases it is believed
plate.
that the genital tubercle is formed caudal
The penile urethra formed in this way to the urogenital membrane instead of
extends only up to the glans penis. The being ventral to it. When the membrane
distal-most part of the urethra is of ruptures, the urogenital sinus opens cranial
ectodermal origin and is formed by to the developing penis.
canalization of a solid mass of ectodermal
Other anomalies of the penile urethra have
cells (Figs 16.26G, H).
(e) The genital swellings fuse with each other, been described earlier.
in the midline, to form the scrotal sac into
Path taken by
which the testes later descend. primordial germ cells
to reach gonad Mesentery
Prenatal Diagnosis of Sex
The sex of a baby can be determined before
birth by ultrasound examination. The penis can
be seen in a male child.
In this connection it has to be noted that in
fetuses about three to four months old, the
genital tubercle is equally developed in both
the male and female. Ultrasound examination
at this stage can be misleading as the clitoris
can be mistaken for a penis.
Yolk sac
Anomalies of M a l e External Genitalia
Fig. 16.28 Migration of primordial germ cells from
1. The entire penis may be absent.
the neighbourhood of the yolk sac to the
Alternatively the corpora cavernosa or the developing gonad.
Human Embryology
Primordial
germ celfs
Thickened coelomic
epithelium forming
genital ridge
Mesonephric duct
becomes duct of
epididymis Mesonephric Primordial follicles
, tubules forming
V—. vasa efferentia
C Rete-
O
testis
Seminiferous
tubules formed
by canalization
of sex cords Germinal epithelium
Fig. 16.29 Development of gonads. (A) Indifferent stage. (B) and (C) Testis. (D) and (E) Ovary.
Urogenital System
Anomalies of Female External Genitalia that covers the medial side of the mesonephros, of
the corresponding side (Fig. 16.29). In the region
1. The clitoris may be absent, may be bifid, where the testis is to develop, this germinal
or may be double. It may be enlarged in epithelium becomes thickened. This thickening is
hermaphroditism. called the genital ridge. The cells of the germinal
2. The labia minora may show partial fusion. epithelium proliferate and form a number of solid
3. The urethra may open on the anterior wall sex cords, that grow into the underlying
of the vagina; this is the female equivalent mesenchyme. They reach deep into the gonad and
of male hypospadias. are called medullary cords. They are soon
canalized to form the seminiferous tubules.
Meanwhile, the primordial germ cells migrate to
Primordial Germ Cells (Fig. 16.28)
the region of the developing testis and get
The cells of the ovaries and the testes, from which incorporated in the seminiferous tubules.
germ cells are formed, are believed to be
segregated early in the life of the embryo. The interstitial cells of the testis, are derived
They probably differentiate in the wall of the from sex cords that are not canalized. Some of
yolk sac and migrate to the region of the them are also derived from the surrounding
developing gonads. mesenchyme.
All spermatozoa and ova that are formed The mesenchymal cells, surrounding the
throughout the life of the individual are believed developing testis, form a dense layer of fibrous
to arise from these primordial germ cells. tissue. This is the tunica albuginea. It
Gonads do not develop as long as primordial completely separates the sex cords from the
germ cells do not reach them. These cells have an germinal epithelium and, thereafter, this
inducing erred on rhc gonad. epithelium can make no further contribution to
testicular tissue.
Hach testis develops from the coelomic epithelium, We have seen, above, that the testis develops in
Seminiferous
tubules Seminiferous
tubule
Fig. 16.30 Development of duct system of the testis. Structures derived from sex cords are shown in grey.
Human Embryology
Descent of Testes
The testes develop in relation to the lumbar region
of the posterior abdominal wall. During fetal life,
theyigradually descend to the scrotum. They reach
Fig. 16.31 Descent of the testis (from the lumbar
the iliac fossa during the third month, and lie at
region to the scrotum),
the site of the deep inguinal ring up to the seventh
month of intrauterine life. They pass through the
close proximity to the mesonephros and the inguinal canal during the seventh month, and are
mesonephric duct. We have also seen that most of normally in the scrotum by the end of the eighth
the mesonephric tubules degenerate. Some of these month (Fig. 16.31).
that lie near the testis persist and, along with the
mesonephric duct, form the duct system of the testis
(Fig. 16.30). The descent of the testes is caused or assisted
by several factors. These are:
The ends of the seminiferous tubules anastomose
with one another to form the rete-testes. The rete- 1. Differential growth of the body wall.
Peritoneum
Transversus abdominis
and internal oblique m.
Skin
F. transversalis
Gubernaculum
Fig. 16.33 Relation of descending testis to processus vaginalis. Note that as the testis descends it
progressively invaginates the processus vaginalis.
into the gubernacular mesenchyme of the the scrotum. Some interesting facts about
inguinal canal and of the scrotum (Fig. 16.32). this condition are as follows:
As the testis descends, it invaginates the
(a) The testis may complete its descent
processus vaginalis from behind. After the
descent of the testis is completed, the after birth.
processus vaginalis loses all connection (b) Spermatogenesis often fails to occur
with the peritoneal cavity and becomes the in an undescended testis.
tunica vaginalis (Fig. 16.33). (c) An undescended testis is more likely
5. The descent of the testis is greatly to develop a malignant tumour than
influenced by hormones secreted by the a normal testis.
pars anterior of the hypophysis cerebri. (d) The condition can be surgically
corrected.
Anomalies of Testis 5. Abnormal positions (Ectopia): The testis
1. The testis may be absent, on one or both may lie (Fig. 16.34):
sides. (a) Under the skin of the lower part of the
2. The testis may be duplicated. abdomen.
3. The two testes may be fused together. (b) Under the skin of the front of the thigh.
4. Anomalies of descent (Cryptorchidism): (c) In the femoral canal.
Descent of the testis may fail to occur, or (d) Under the skin of the penis.
may be incomplete. The organ may lie in (e) In the perineum behind the scrotum.
the lumbar region, in the iliac fossa, in
the inguinal canal, or in the upper part of 6. Also see hermaphroditism.
Fig. 16.35 Anomalies of processus vaginalis. Abnormal persistence of the processus vaginalis can lead to
hernia (passage into it of abdominal contents, indicated by arrows); or hydrocoele (collection of
fluid, shown as dots). Various types of hernia and hydrocoele are s h o w n .
Urogenital System
Uterine tube
Epoophoron U{enj&
Ovary
Paradidymis
Epididymis
Fig. 16.37 Some structures derived from the mesonephric ducts. (A) In the male these are the epididymis, the
ductus deferens, the seminal vesicles and ejaculatory ducts. The appendix of the epididymis is a
vestigial remnant. (B) In the female most of the duct disappears. Some remnants are seen as the
epoophoron. For complete list of derivatives of the mesonephric ducts see text.
Human Embryology
Vestigial Structures in the Region of the Testis germinal epithelium may contribute to the
ovary even in postnatal life.
A number of vestigial structures are to be seen
in the n e i g h b o u r h o o d of t h e testis. T h e i r
Descent of the Ovary
importance lies in the fact that any one of them
may enlarge to form a cyst. The ovary descends from the lumbar region,
These structures are: where it is first formed, to the true pelvis. A
g u b e r n a c u l u m f o r m s , as in the m a l e , a n d
(a) Appendix of testis (also called hydatid
extends from the ovary to the labium majus. It
of Morgagni).
becomes attached to the developing uterus at
(b) Appendix of epididymis. its junction with the uterine tube. T h e part of
(c) Superior aberrant ductules. the gubernaculum that persists between the
(d) Inferior aberrant ductules. ovary a n d the uterus becomes the (round)
(e) Paradidymis.
ligament of the ovary. The part between the
uterus and the labium majus becomes the round
DEVELOPMENT OF THE OVARY ligament of the uterus.
Table 16.1 Summary of male and female homologues derived from undifferentiated genital system
posterior wall of the female urethra, is also derived We have already seen t h a t individuals
from them. with t w o X - c h r o m o s o m e s are female,
while those with one X-chromosome and
The mesonephric ducts and tubules do n o t one Y-chromosome are male.
establish any connection with the developing 2. T h e Y-chromosome bears a gene (SRY
ovary. However, they give rise to some vestigial g e n e , p r e s e n t o n s h o r t a r m ) t h a t is
structures seen in the broad ligament near the responsible for p r o d u c t i o n of a testis
ovary. determining factor. This factor plays a vital
These vestigial structures (Fig. 16.37B) are role in causing the developing gonad to
as follows: become a testis. Apart from a direct action
on the gonad, this factor influences other
(a) Epoophoron: This consists of a longitudi-
genes (SOX-9) t h a t play a role in the
nal duct running parallel to the uterine
process. Under the influence of these genes,'
tube, and a number of transverse ductules
Sertoli cells are formed from cells of the
that open into the longitudinal duct. It
sex cords and Ley dig cells are formed from
corresponds to the epididymis and vasa
mesenchymal cells of the gonadal ridge.
efferentia of the male (Note that the word
' e p o o p h o r o n ' means 'above egg basket': 3. Once the testis is formed, the interstitial
ep = above, oo = egg, and photon = basket). (Leydig) cells in it begin t o p r o d u c e
t e s t o s t e r o n e ( u n d e r t h e i n f l u e n c e of
In some cases the longitudinal duct is
gonadotropins formed in the placenta).
unusually long. It runs along the side of
This testosterone influences the
the u t e r u s , and lower d o w n , becomes
differentiation of genital ducts and external
embedded in the wall of the cervix. It, how-
ever, never opens into the uterine lumen. genitalia. By the end of eighteenth week
It is the equivalent of the male ductus fetal Leydig cells disappear to reappear
deferens and is also called Gartner's duct. only at the time of puberty.
4. Supporting cells in the fetal testis (Sertoli
(b) Paroophoron; This consists of small blind
tubules between the ovary and the uterus, cells) p r o d u c e a Mullertan inhibiting
a n d is t h e female e q u i v a l e n t of t h e substance. This substance causes regression
paradidymis. The word paroophoron of paramesonephric ducts. The Sertoli cells
means 'near egg basket*. also secrete an androgen binding factor
that helps in formation of spermatozoa
from spermatogonia.
Control of Differentiation of Genital Organs
As the Y-chromosome is missing in a female
From the account of the development of the
fetus, none of the processes described above take
gonads and genitalia, it is seen that these organs
place. The ovary is formed under the influence
are derived from the same primordia in both
of the W N T 4 gene. The oestrogens (derived from
sexes. The male and female genital systems are
maternal and placental sources) influence the
identical till the beginning of seventh week of
formation of internal and external genital organs.
intrauterine life. T h e factors t h a t determine
whether these organs will develop as in the male,
or as in the female are as follows: Hermaphroditism
Abnormal development of the gonad and the
1. T h e m o s t i m p o r t a n t f a c t o r is t h e genitalia gives rise to various types of herma-
chromosomal sex of the individual, which phroditism. A hermaphrodite is in fact a person
is determined at the time of fertilization. w h o is both a male and a female at the same
Urogenital System
Neural crest
Neural crest Neural groove \ N e u r a | tube
Fig. 17.1 Formation of neural tube. (A) Embryonic disc before formation of neural plate.
(B) Neural plate f o r m e d by thickening of ectoderm. (C) Neural plate is
converted to a groove. (D) The groove is converted to a tube. Note the neural
crest w h i c h lies along the edges of the neural plate (B), or neural groove (C).
After formation of the neural tube the neural crest lies dorsal to it (D).
Human Embryology
and a caudal tubular part (Fig. 17.2A). The developed from each of these divisions of the neural
enlarged cranial part forms the brain. The caudal tube are as follows (Fig. 17.2):
tubular part forms the spinal cord: it is at first The prosencephalon, mesencephalon and
short, but gradually gains in length as the embryo rhombencephalon are at first arranged cranio-
grows. The cavity of the developing brain soon caudally (Fig. 17.3A). Their relative position is
shows three dilatations (Fig. 17.2B). Cranio- greatly altered by the appearance of a number of
caudally, these are the prosencephalon, flexures. These are:
mesencephalon and rhombencephalon. The
prosencephalon becomes subdivided into the (a) the cervical flexure, at the junction of the
telencephalon and the diencephalon (Fig. 17.2C). rhombencephalon and the spinal cord
The telencephalon consists of right and left (Fig. 17.3B);
telencephalic vesicles. The rhombencephalon also (b) the mesencephalic flexure (or cephalic
becomes subdivided into a cranial part, the flexure); in the region of the midbrain
metencephalon and a caudal part, the (Fig. 17.3C);
myelencephalon. The parts of the brain that are (c) the pontine flexure, at the middle of the
Cerebral cortex
Telencephalon
Corpus striatum
Thalamus
Prosencephalon Hypothalamus Cerebral
hemisphere
Diencephalon Optic stalk
Pars nervosa of
hypophysis cerebri
Mesencephalon Midbrain
<
Telencephalon
Diencephalon
Mesencephalon
• Spinal
cord
< Metencephalon
Myelencephalon
rhombencephalon, dividing it
Rhombencephalon Prosencephalon info the metencephalon and
Mesencephalon
myelencephalon (Fig. 17.3D);
and
(d) t h e telencephalic flexure,
which occurs much later
between the telencephalon and
diencephalon.
Telencephalon
Mesencephalon
Cerebellum
- Myelencephalon
Telencephalon
Diencephalon
Mesencephalon
-Metencephaion
Metencephaion
(Pons)
Myelencephalon Myelencephalon
(Medulla)
Fig. 17.4 Development of external form of the h u m a n brain. Note progressive overlapping of diencephalon
and mesencephalon by the expanding telencephalon.
Telencephalon
Lateral ventricle (Cerebral hemisphere)
Third ventricle
Cerebral aqueduct
Fourth ventricle
Rhombencephalon
(Metencephalon +
Myelencephalon)
Central canal
Postganglionic
sympathetic
neurons
^J\j0 Schwann cell
M
Adrenal medulla
Dorsal nerve root
ganglion cells
Y
(and other sensory ganglia)
Fig. 17.6 Traditionally recognized derivatives of the neural crest. Many additional
derivatives are now recognized (as mentioned in the text).
neural crest are believed to migrate into the musculature of the head, and in formation of
mesenchyme of the head and neck and influence the face.
development of somitomeres. They probably Other structures believed to arise from the
play an important role in development of the neural crest are as follows.
Human Embryology
(a) Pia-mater and arachnoidmater. in the dorsal part. As a result, the ventral part of
(b) Mesenchyme of dental papilla, o d o n t o - the lumen of the neural tube becomes compressed.
blasts and dentine. The line separating the compressed ventral part,
(c) Bones of the face and part of the vault of from the dorsal part, is called the sulcus limitans
skull (frontal, parietal, squamous tempo- (Fig. 17.7C). With its formation, the lateral wall
ral, part of the sphenoid, maxilla, zygoma- of the developing spinal cord can be divided into
tic, nasal, vomer, palatine and mandible). a dorsal part, called the dorsal or alar lamina and a
(d) Dermis, smooth muscle and fat of face and ventral part, called the ventral or basal lamina.
ventral aspect of neck. This division is of considerable functional
(e) Muscles of the ciliary body. i m p o r t a n c e . T h e basal lamina develops into
(f) Sclera and choroid of eye (?). structures that are motor in function, and the alar
(g) Substantia propria and posterior epithe- lamina into those that are sensory. The alar and
lium of cornea. basal laminae are also called the alar and basal
(h) Connective tissues of thyroid, parathyroid, plates respectively.
thymus and salivary glands, With continued g r o w t h in thickness of the
(i) Derivatives of the first, second and third mantle layer, the spinal cord gradually acquires
pharyngeal cartilages. its definitive form (Figs 17.7D, E). With growth
(j) C cells of the thyroid gland, of the alar lamina, the dorsal part of the cavity
(k) C a r d i a c s e m i l u n a r valves, a n d c o n o - within the cord becomes obliterated: the posterior
truncal septum (spiral septum plus bulbar median septum is formed in this situation. The
septum). ventral part of the cavity remains as the central
canal. Further enlargement of the basal lamina
Clinical Correlation causes it to project forwards on either side of the
midline, leaving a furrow, the anterior median
Several diseases and syndromes are associated
with d i s t u r b a n c e s of the neural crest, i.e. fissure, between the projecting basal laminae of
H i r s c h s p r u n g ' s disease (aganglionic mega- the two sides.
colon), a o r t i c o p u l m o n a r y septal defects of The nerve cells that develop in the mantle zone
h e a r t , cleft l i p , cleft p a l a t e , f r o n t o n a s a l of the basal lamina become the neurons of the
d y s p l a s i a , n e u r o f i b r o m a t o s i s , t u m o u r s of anterior grey column (Fig. 17.8). The axons of
adrenal medulla, albinism, etc. these cells grow out of the ventrolateral angle of
the spinal cord to form the anterior nerve roots of
the spinal nerves. The nerve cells that develop in
SPINAL CORD the mantle layer of the alar lamina form the
neurons of the posterior grey column. These are
The spinal cord is developed from the caudal sensory neurons of the second order. Their axons
cylindrical part of the neural tube. travel predominantly u p w a r d s in the marginal
When this part of the neural tube is first formed, layer to form the ascending tracts of the spinal
its cavity is in the form of a dorsoventral cleft. cord. Many of these cells form interneurons.
The lateral walls are thick, but the roof (dorsal) The dorsal nerve roots are formed by the axons
and the floor (ventral), are thin (Fig. 17.7A). The of cells t h a t d e v e l o p from t h e n e u r a l c r e s t
wall of the tube subdivides into the matrix cell or (Figs 17.6, 17.8). Groups of these cells collect on
e p e n d y m a l layer, the m a n t l e layer a n d t h e the dorsolateral aspect of the developing spinal
marginal layer (Fig. 17.7B) as already described. cord to form the dorsal nerve root ganglia (or
The mantle zone grows faster in the ventral spinal ganglia). The axons of these cells divide
part of the neural tube and becomes thicker, than into t w o . The central processes migrate t o w a r d s
The Nervous System
Ependymal layer
Fig. 17.7 Development of spinal cord. (A] Single layered neural tube. (B) Ependymal, mantle and marginal
layers established. (C) & (D) Mantle layer divided into alar and basal laminae. (E) Ventral and
dorsal grey columns established. The dorsal part of the cavity of the neural tube disappears. The
ventral part persists as the central canal.
the spinal cord and establish contact with the the same time, axons of cells developing in various
dorsolateral aspect of the latter, thus forming the parts of the brain grow d o w n w a r d s to enter the
dorsal nerve roots. These axons finally synapse marginal layer of the spinal cord and form its
w i t h n e u r o n s of the p o s t e r i o r grey c o l u m n descending tracts. These ascending and descending
developing in the alar lamina. T h e peripheral tracts form the white matter of the spinal cord. As
processes of the cells of the dorsal nerve r o o t the mantle layer takes on the shape of the anterior
ganglia g r o w o u t w a r d s to form the s e n s o r y and posterior grey columns, the white matter
components of the spinal nerves. becomes subdivided into anterior, lateral a n d
As stated above, the axons of neurons in the posterior white columns.
posterior grey column enter the marginal layer, The spinal cord at first extends throughout the
to form the ascending tracts of the spinal cord. At l e n g t h of t h e d e v e l o p i n g v e r t e b r a l c a n a l
Human Embryology
^ s t
Marginal f X ~ ^
layer \c_^*^~
Mantle layer
Opposite third
lumbar vertebra
at full term
Fig. 17.9 Recession of spinal cord. Note that the lower end of the cord gradually move cranially, relative to
the vertebrae.
The Nervous System
{Fig. 17.9A). Subsequently, however, the vertebral O n e effect of this recession (of the cord) is that
column becomes much longer than the spinal cord, the intervertebral foramina no longer lie at the
with the result that at full term the lower end of level at which the corresponding spinal nerves
the cord is at the level of the third lumbar vertebra emerge from the spinal cord (Fig. 17.10). The
(Figs 17.9B, C). This process of recession of the nerves h a v e , t h e r e f o r e , t o follow an o b l i q u e
spinal cord continues after birth as a result of d o w n w a r d course to reach the foramina. This
which, in an adult, the cord usually ends at the obliquity is least for the cervical nerves, a n d
level of the lower b o r d e r of the first l u m b a r greatest for the sacral and coccygeal nerves.
vertebra.
MEDULLA OBLONGATA
Marginal layer
Bulbo-pontine
extension
Olivary nucleus
and descending tracts that pass through the gives origin to the sensory cranial nerve nuclei,
medulla. and the basal lamina to the motor cranial nerve
nuclei, of the pons (Figs 17.12, 17.13). Their
PONS derivation is illustrated in Figs 17.12 and 17.13.
The nuclei derived from the basal and alar,
The pons arises from the ventral part of the laminae lie in the dorsal or tegmental parr of the
metencephalon. It also receives a contribution from pons. The ventral part of the pons is constituted
the alar lamina of the myelencephalon, in the form by:
of the cranial part of the bulbo-pontine extension
(Figs 17.12, 17.13, 17.15). This extension comes (a) Cells of the bulbo-pontine extension (derived
to lie ventral to the metencephalon, and gives rise from the alar lamina of the myelence-
to the pontine nuclei. Axons of cells in these nuclei phalon), that form the pontine nuclei. Axons
grow transversely to form the middle cerebellar of the cells in these nuclei grow transversely
peduncle. and form the middle cerebellar peduncle.
As in the myelencephalon, the roof of the (b) Corticospinal and corticobulbar fibres
metencephalon becomes thin and broad descend from the cerebral cortex and pass
(Figs 17.12, 17.13). The alar and basal laminae through this region on their way to the
are thus orientated as in the medulla. medulla and spinal cord. Some fibres from
The lateral part of each alar lamina (often called the cerebral cortex terminate in relation to
the rhombic lip) becomes specialized to form the the pontine nuclei. These are the cortico-
cerebellum. The ventral part of the alar lamina pontine fibres.
The Nervous System
Somatic efferent
MIDBRAIN
PONS SAL
t
I' ^07 Cochlear
Open
part
10
Closed 12 10
part
Fig. 17.12 Functional classification of cranial nerve nuclei. The upper figure shows the
arrangement of nuclear columns in the brainstem of the embryo. The lower figure
shows the nuclei derived from each column. Numbers indicate cranial nerves connected
to the nuclei.
Human Embryology
Fig. 17.13 Location of cranial nerve nuclei as seen in transverse sections at various levels of the
brainstem.
The Nervous System
MIDBRAIN
Fig. 17.16 Structu of the brainstem derived from alar and basal laminae.
Alar lamina
and basal lamina
of metencephalon
Lateral
hemisphere
Fig. 17.17 Some stages in the development of the cerebellum. (A) Cerebellar rudiments appear from
alar lamina of metencephalon. (B) They grow into the roof plate of the metencephalon to
meet in the m i d l i n e . (C) Cerebellum enlarges and bulges out of the fourth ventricle.
(D) Lateral hemispheres and vermis can be distinguished.
The Nervous System
Prosencephalon before
Coronal section
appearance of
through A
telencephalic diverticulum
Coronal Section
through B
Fig. 17.18 Development of the cerebral hemisphere. This series of figures shows the
changes in the relative size and position of the diencephalon and the
telencephalic vesicles. Figures (A), (B), (C) and (D) are lateral views.
Figures (E), (F), (G) and (H) are corresponding coronal sections along the axes
indicated. (A), (E) Prosencephalon before appearance of telencephalic vesicles.
(B), (F) Telencephalic vesicles appear. (C), (G) Telencephalic vesicles enlarge
and partially cover diencephalon. (D), (H) Telencephalon m u c h larger than
diencephalon and completely overlapping it.
Human Embryology
© Outline of
Cerebral hemisphere ventricle
Choroid fissure
(red line)
Fig. 17.20 Establishment of the form of the cerebral hemisphere and of the lateral ventricle. Arrows indicate
direction of growth. The c h o r o i d fissure is shown in dotted line.
The Nervous System
Wall of telencephalon
Lateral ventricle
Choroid fissure
farrows)
Diencephalon
Fig. 17.21 Formation of the choroid fissure. The wall of the telencephalon remains thin at
this site.
Fig. 17.22 Formation of telachoroidea (fold of pia mater) and choroid plexus (bunch of
capillaries).
Human Embryology
(Figs 1 7 . 1 8 B , F), b u t rapidly increase in size Each lateral ventricle is at first a spherical space
extending u p w a r d s , f o r w a r d s and b a c k w a r d s within the telencephalic vesicle (Fig. 17.20A).
(Figs 17.18,17.19). As a result of this enlargement, With the forward and backward growth of the
the telencephalon comes to completely cover the late- vesicle, t h e v e n t r i c l e b e c o m e s e l o n g a t e d
ral surface of the diencephalon (Figs 17.18D, H) anteroposteriorly (Fig. 17.20B). The posterior
and eventually fuses with it (Fig. 17.19). Thus, end of the telencephalic vesicle n o w g r o w s
the cerebral cortex and corpus striatum come to downwards and forwards, to form the temporal
lie lateral to the thalamus and hypothalamus. lobe, a n d the cavity within it becomes the
With further upward, forward and backward inferior horn (Figs 17.20C, D). T h e ventricle
extension of the telencephalic vesicles, the vesicles thus becomes C-shaped. Finally, as a result of
of the two sides come into apposition with each b a c k w a r d g r o w t h , the occipital pole of the
o t h e r a b o v e , in f r o n t of, a n d b e h i n d t h e hemisphere becomes established, the part of the
diencephalon (Figs 17.18H, 17.19). ventricle within it becoming the posterior horn
The cavity of the diencephalon forms the third (Fig. 17.20E).
ventricle, w h i l e t h e c a v i t i e s of t h e t w o From Fig. 17.18H it will be seen that, with
telencephalic vesicles form the lateral ventricles the enlargement of the telencephalic vesicles,
(Fig. 17.5). their medial walls become apposed to each
Epithalamic sulcus
Pineal evagination
Wall of diencephalon
— Epithalamus
—Thalamus
Hypothalamus
Hypothalamic
sulcus v
Hypothalamus
Interventricular foramen N
Evagination for neurohypophysis
Epithalamic sulcus
Epithalamus
Aqueduct
Floor of third ventricle
Neurohypophysis
Fig. 17.23 Development of thalamus and hypothalamus- The appearance of the epithalamic and
hypothalamic sulci divides the diencephalon into thalamus, epithalamus and hypothalamus.
The pineal body is formed in relation to the epithalamus, and the neurohypophysis in relation
to the hypothalamus.
The Nervous System
3rd ventricle
Lat. ventricle
Telencephalon
Diencephalon
Fig. 17.24 Early development of corpus striatum as seen i n coronal sections. (A) Telencephalon before
appearance of corpus striatum. (B) W a l l of basal part thickened. (C) Thickening divides into
medial and lateral parts.
Wall of telencephalon
Lateral ventricle
Cerebral cortex
Corpus striatum
(Superficial part)
Fig. 17.25 Wall of telencephalon at a stage somewhat later than that shown in Fig. 17.30C. The region of the
developing corpus striatum is divided (longitudinally) into deep and superficial parts (by nerve
fibres growing downwards through it).
Human Embryology
other. In this way a groove bounded by the two lateral ventricle, the choroid fissure becomes
medial surfaces is formed, these surfaces being C-shaped (Fig. 17.20). The inferior part of the
continuous with each other in the floor of the fissure now invaginates into the inferior horn
groove. Note that the floor of this groove forms of the lateral ventricle (Fig. 17.20E).
the roof of the third ventricle. Just above the
floor of t h i s g r o o v e , t h e m e d i a l w a l l is
invaginated laterally into the cavity of the
Thalamus and Hypothalamus
lateral ventricle. The cavity of the invagination The thalamus and hypothalamus develop from the
is the choroid fissure (Fig. 17.21). A fold of pia d i e n c e p h a l o n . After the e s t a b l i s h m e n t of the
mater extends into this fissure and forms the telencephalon, the lateral wall of the diencephalon
telachoroidea. A bunch of capillaries is formed becomes thickened. It is soon subdivided into three
within this fold and forms the choroid plexus regions by the appearance of two grooves, called
(Fig. 17.22). The original wall of the ventricle the cpithalamic and hypothalamic sulci
lining the choroid plexus, remains very thin (Fig. 17.23A). The central part, lying between these
and forms the ependymal covering of the plexus t w o s u l c i , e n l a r g e s t o form t h e thalamus
(Fig. 17.22). Note that the telachoroidea is in (Figs 17.23B, C). The parr above the cpithalamic
intimate relationship with both lateral ventricles sulcus remains relatively small and forms the epi-
and also with the roof of the third ventricle thalamus, which is represented by the habenular
(Fig. 17.22). nuclei and the pineal body. The part below the
With the establishment of the temporal pole hypothalamic sulcus forms the hypothalamus.
and the formation of the inferior horn of the T h e v a r i o u s nuclei of t h e t h a l a m u s a n d
Lateral ventricle
Developing
" cerebral cortex
- Lentiform nucleus
Third _
ventricle
Fig. 17.26 Deep part of corpus striatum becomes the caudate nucleus. Superficial part
becomes the lentiform nucleus. Note the relation of these to the thalamus
developing in the diencephalon.
The Nen/ous System
hypothalamus are formed by multiplication of cells pass through the region of the corpus striatum
in the mantle layer of the wall of the diencephalon. and divide it into a deeper and a superficial
part. These fibres constitute the internal capsule
(Fig. 17.25).
Corpus Striatum
The part of the corpus striatum that comes
T h e c o r p u s s t r i a t u m is a d e r i v a t i v e of t h e to lie deep to the internal capsule, becomes the
telencephalon. Early in its d e v e l o p m e n t each caudate nucleus, a n d the superficial p a r t
telencephalic vesicle can be subdivided into a basal becomes the lentiform nucleus (Fig. 17.26).
part which is thick and a superior part which is T h e lentiform n u c l e u s later b e c o m e s s u b -
thin (Figs 17.24A, B). Some of the cells, in the divided i n t o the putamen a n d the globus
mantle layer of the thick basal part, migrate into pallidus.
the overlying marginal layer to form part of the
cerebral cortex. The remaining cells of the mantle
Cerebral Cortex
layer of this region form the corpus striatum.
The cerebral cortex is formed by migration of cells
The developing corpus striatum soon becomes from the mantle layer into the overlying marginal
subdivided into medial and lateral subdivisions, layer. These cells divide and subdivide, leading
which increase in thickness (Fig. 1 7 . 2 4 C ) . to considerable thickening of the cortex. By full
Meanwhile, the cerebral cortex is developing term, several layers of cells can be recognized.
and numerous axons, that are growing Simultaneously, there is considerable side to side
d o w n w a r d s from it, or are growing towards it, expansion of the cortex as a result of which its
Caudate nucleus
Cerebral cortex
Thalamocortical
fibres
Corpus -
callosum
Internal _
capsule
Fig. 17.27 W i t h enlargement of the telencephalon the lentiform nucleus comes to lie lateral
to the thalamus. The internal capsule passes through the interval between the
lentiform nucleus laterally and the caudate nucleus and thalamus medially.
Human Embryology
A f
Interventricular
•
\ — •
m \ _ )
foramen
Hippocampal cortex
""N. Developing
" V ^ corpus callosum
\ .
B
( ((
/ ^ / ^
•—'
Interventricular
foramen
Choroid fissure (Dots;
c
I Q- • x ~J Corpus callosum
/ ^ Interventricular foramen
Dentate gyrus \
Hippocampus
surface area is greatly increased. As the surface part. It undergoes very great expansion and forms
expansion is at a greater rate than that of the hemi- the whole of the cerebral cortex seen on the
sphere as a whole, the cortex becomes folded on superolateral and medial surfaces of the cerebral
itself. Sulci and gyri are formed as a result of this hemisphere, and the cortex of the inferior surface
folding. The region of the insula is relatively slow excluding the pyriform area (Fig. 17.29B). The
in growth and is gradually overgrown by adjacent hippocampal cortex forms the hippocampus and
areas, which form the opercula of the insula. the indusium griseum. The piriform cortex gives
From the developmental point of view, the rise to the parr of rhe cerebral cortex that receives
cerebral cortex consists of: (a) the hippocampal olfactory sensations. It forms the uncus, the anterior
cortex, (b) the pyriform cortex, and (c) the part of the parahippocampalgyrus and the anterior
neocortex. The neocortex is the most important perforated substance.
The Nervous System
Hippocampal Neocortex
Neocortex
cortex >
\ \ /
W Lateral
ventricle
\ \
\ \
Indusium J
> /
griseum \ ] f [
White
matter
Thalamus—4-
5Wi ^ ' B
Fig. 17.29 Development of the cerebral cortex. Most of the cerebral cortex is derived from the neocortex.
The hippocampal cortex forms the hippocampus and the indusium griseum. The piriform cortex
forms part of the limbic system.
The developing telencephalon has a medial wall From Figs 17.28, 17.29A it will be seen that
(apposed to its counterpart of the opposite side), the hippocampal cortex is closely related to the
a superolateral wall and a basal striatal region choroid fissure. With the establishment of the
(Fig. 17.24C). The hippocampal cortex develops inferior horn of the lateral ventricle, the
in the medial wall, the pyriform cortex in the hippocampal cortex follows the curve of
marginal layer superficial to the corpus the choroid fissure and thus assumes a ring-
striatum, and the neocortex in the superolateral like configuration (Fig. 17.28R). However, the
region (Fig. 17.29A). superior part of the hippocampal cortex is soon
Lateral ventricle
Lamina terminalis
forming a path for
fibres crossing from
one side to the other
separated from the fissure by the formation of (a) axons of cortical cells that grow towards
the corpus callosum. This part of the cortex other areas of the cortex, either in the same
remains rudimentary and forms the indusium or in the opposite hemisphere;
griseum. The lower part of the hippocampal (b) axons of cortical cells that grow downwards
cortex undergoes relatively greater develop- through the hemisphere, on their way to the
ment and becomes the hippocampus and the brain stem and spinal cord;
dentate gyrus (Fig. 17.2 8 C). With the expansion (c) axons that connect the thalamus,
of the neocortex (see below), these structures hypothalamus and basal ganglia to one
are pushed into the cavity of the inferior horn another and to the cortex; and
of the lateral ventricle (Fig. 17.29B). (d) axons that grow into the hemisphere from
the brainstem and spinal cord.
White Matter of Cerebrum Cerebral Commissures
The bulk of the cerebrum is constituted by its white The part of the wall of the neural tube that
matter. This is made up of: closes the cranial end of the prosencephalon is
_ Lamina
terminals
Interventricular
foramen
Junction between
R. and L. telencephalic Cerebral hemisphere
hemispheres (Medial surface)
Corpus callosum
Wall of third beginning to form
ventricle
Septum lucidum
Corpus callosum
Septum lucidum
Anterior commissure
Q ventricle •* Lamina terminalis
Aqueduct - Optic chiasma
Interventricular foramen' Hypophysis cerebri
Neural tube
not formed
Pia-arachnoid
\ — ^ Dilated
/^y-^ytf Neural tube
Ski Durama,or
/ (0\r
Fig. 17.32 Anomalies of the neural tube. (A) Posterior rachischisis. (B), (C) and (E)
Varieties of meningo-myelocoele. (D) Meningocoele.
called the lamina terminalis (Figs 17.30, Anomalies of the Brain and
17.37A). After the appearance of the the Spinal Cord
telencephalic vesicles, the lamina terminalis lies
Non-closure of Neural Tube
in the anterior wall of the third ventricle.
Examining Fig. 17.30 will show that any neuron 1. Posterior rachischisis: The whole length
growing from one hemisphere to the other must of the neural tube remains unclosed
pass through this lamina. To facilitate this (Fig. 17.32A).
passage, the lamina terminalis becomes 2. Anencephaly: The neural tube remains
thickened to form the commissural plate open in the region of the brain. The
(Fig. 17.31B). exposed brain tissue degenerates.
The first commissural fibres to develop form 3. Non-fusion of the neural tube is of
the anterior commissure. This is followed by necessity associated with non-closure of
the formation of the hippocatnpal commissure. the cranium {cranium bifidum) or of the
The corpus callosum appears later. It, at first, vertebral canal {spina bifida, Fig. 17.32A).
lies anterior to the diencephalon, but because
of rapid increase in its size it extends backwards Outward Bulging of Neural Tube and
and roofs over this region (Fig. 17.31C). Covering Membranes
Other commissures that appear are the optic As a result of non-fusion of the neural tube, or
chiasma, the babcnular commissure and the of overlying bones (e.g. spina bifida), neural
posterior commissure. tissue may lie outside the cranial cavity or
Human Embryology
vertebral canal. When this happens in the region the overlying bones, the neural tissue is
of the brain the condition is called covered by bulging skin and membranes
encephalocoele and when it occurs in the spinal {meningo-mylocoele) (Figs 17.32B, C, E).
region it is called myelocoele (Figs 17.32B, C). 3. Occasionally the bulging is caused by the
membranes alone {meningocoele), the
1. When the condition is due to non-closure neural tissue being normally located
of the neural tube, nervous tissue is (Fig. 17.32D). Some varieties of these con-
exposed on the surface, as in anencephaly ditions are illustrated in Figs 17.32B - F..
and in rachischisis (Fig. 17.32A).
2. When the neural tube has closed and the When a meningo-myelocoele is present, the
outward bulging is a result of a defect in medulla oblongata, and the tonsils of the
Preganglionic neurons
White ramus
communicans "
Ganglion containing
postganglionic neurons
TO BLOOD VESSELS
HAIR & SWEAT GLANDS Visceral or
• collateral
ganglion
Sympathetic ganglion—*-;
cerebellum, are displaced caudally into the Similar enlargement of the spinal cord is called
foramen magnum causing obstruction to the hydromyelia; the enlargement of the central
flow of cerebrospinal fluid. This leads to canal being called syringocoele. This condition
hydrocephalus. These conditions together may be associated with the formation of
constitute the Arnold Chiari deformity. abnormal cavities near the central canal
[syringomyelia). Destruction of nervous tissue
Congenital Hydrocephalus at this site results in a characteristic syndrome.
In one form of hydrocephalus, resulting from
An abnormal quantity of cerebrospinal fluid blockage of the median and lateral apertures
may accumulate in the ventricular system of of the fourth ventricle, the enlargement is
the brain (hydrocephalus). This may be due to predominantly in the posterior cranial fossa,
a blockage to its flow or to excessive production. and the cerebellum is abnormal (Dandy Walker
The ventricles become very large and the infant syndrome). Obstruction to flow of cerebrospinal
is born with a large head. The pressure of the fluid may also be caused by stenosis or
fluid causes degeneration of nervous tissue. malformation of the cerebral aqueduct.
Preganglionic neurons
in general visceral efferent
nucleus in brain stem
Fig. 17.34 Development of preganglionic and postganglionic parasympathetic neurons. (A) Cranial outflow.
(B) Sacral outflow.
Human Embryology
Hypophysis Cerebri,
Pineal, Adrenal
HIGHLIGHTS
• T h e p a r s a n t e r i o r a n d i n t e r m e d i a of the
hypophysis cerebri develop from Rathke's
p o u c h . T h e p a r s nervosa develops from a
downgrowth arising from the floor of the third
ventricle.
• The pineal gland develops as a diverticulum
from the roof of the t h i r d v e n t r i c l e
(diencephalon).
• The adrenal cortex is derived from coelomic
epithelium. The cells of the adrenal medulla
are derived from the neural crest.
HYPOPHYSIS CEREBRI
T h e h y p o p h y s i s cerebri or pituitary gland is
developed from two separate sources.
Pineal evagination
Stomatodaeum
Pars posterior
Pars intermedia
2. The pars nervosa and state of the hypophysis that are seen in relation to the sphenoid bone
cerebri develop from a downgrowth from and the roof of the nasopharynx.
the floor of the third ventricle (dience-
phalon) in the region of the infundibulutn Accessory anterior lobe tissue may be seen in
(Fig. 1 8.1C). This downgrowth comes into relation to the posterior wall of the pharynx.
relationship with the posterior aspect of R a r e l y t h e h y p o p h y s i s m a y fail to d e v e l o p
Rathke's pouch and fuses with it (Fig. 18.1C). (agenesis) or may be underdeveloped (hypoplasia).
Rathke's pouch appears in the third week of
The anterior wall of Rathke's pouch proliferates intrauterine life. It loses contact with the surface
g r e a t l y t o form t h e p a r s a n t e r i o r of t h e epithelium by the second month.
hypophysis. The posterior wall remains thin
and forms the pars intermedia. The original PINEAL GLAND
cleft of Rathke's pouch separates these two parts.
Some cells of the anterior part grow upwards T h e pineal gland (or pineal body) arises as a
along the infundibular stalk to form the tuberal diverticulum from the roof of the diencephalon
part of the hypophysis. (Fig. 18.1A). The outgrowth is at first hollow hut
W i t h t h e f o r m a t i o n of the m o u t h a n d later becomes solid (Fig. 18.2).
p h a r y n x , the original site of a t t a c h m e n t of
Rathke's pouch to the stomatodaeum, comes to The specific cells of the pineal body are believed
lie in the roof of the nasopharynx. Remnants of t o be modified n e u r o g l i a l cells. For long
Rathke's pouch may sometimes give rise to considered to be a vestigeal structure of no
peculiar tumours called craniopharyngiomas importance, the pineal gland is now known to
Human Embryology
r
Pineal evagination -
«r
Cavily of diencephalon -
secrete a n u m b e r of h o r m o n e s t h a t have a T h e d i f f e r e n t i a t i o n of c o r t i c a l z o n e s
regulatory influence on many other endocrine (Fig. 18.3D) begins during the late fetal period.
glands. For details see the author's H U M A N The zona glomerulosa and zona fasciculata are
HISTOLOGY. present at birth but the zona reticularis become
recognizable only at the end of the third year.
The suprarenal of a human fetus is almost of
ADRENAL the same size as that of an adult. It is quite
large as compared to the fetal kidney. The size
The adrenal gland consists of a superficial corrcx of the gland (particularly of fetal cortex)
and a deeper medulla. The cells of the cortex arise b e c o m e s s m a l l e r d u r i n g t h e first year of
from coeloniic epithelium (mesoderm). The cells postnatal life.
of the medulla are derived from the neural crest
The cells of the medulla are derived from
(ectoderm).
the n e u r a l c r e s t . T h e y are s i m i l a r to the
postganglionic sympathetic neurons (cells of
The cells of the cortex arise from the coelomic
sympathetic ganglia). Preganglionic
epithelium that lies in the angle between the
sympathetic neurons terminate in relation to
developing gonad and the attachment of the
them. These cells migrate to the region of the
mesentery (Figs 18.3A). The cells arising from
d e v e l o p i n g c o r t i c a l cells a n d c o m e t o be
the coelomic epithelium may be divided into
surrounded by them.
two groups:
The adrenal gland begins to develop in the
fifth week of intrauterine life.
(a) The cells that are formed first are large
and acidophilic. They surround the cells
of the medulla and form the fetal cortex
Anomalies of Adrenal
(Figs 1 8 . 3 C , D ) . T h e fetal c o r t e x dis- 1. Adrenal cortical tissue may be present at
appears after birth. various ectopic sites.
(b) Subsequently, the coelomic epithelium 2. The entire adrenal may be ectopic and may
gives origin to smaller cells that surround lie deep to the capsule of the kidney. It
the fetal cortex. These smaller cells form may be fused to the liver or the kidney.
the definitive cortex (Figs 1 8 . 3 E , F). 3. T h e r e may be c o n g e n i t a l h y p e r p l a s i a
According to some authorities, the cells of (overdevelopment) of the cortex. In the
the fetal cortex are incorporated into the m a l e this leads t o the adrenogenital
reticular zone of the definitive cortex. syndrome m a r k e d by very e a r l y
Hypophysis Cerebri, Pineal, Adrenal
B
- The cells
derived from
the neural
crest form the
medulla
'"Zona fasciculata
* Zona reticularis
- Degenerating
fetal cortex
HIGHLIGHTS
1
The retina is formed from the optic vesicle, an
outgrowth of the prosencephalon. The optic
vesicle is converted into the optic cup.
The lens of the eye is derived from a thickened
area of surface ectoderm, the lens placode. The
placode is converted into the lens vesicle which
comes to lie in the optic cup.
Other coats of the eyeball are derived from
mesoderm surrounding the optic vesicle. The
epithelium covering the superficial surface of
the cornea is derived from surface ectoderm.
The eyelids are formed by reduplication of
surface ectoderm above and below the cornea.
The lacrimal sac and nasolacrimal duct are
derived from ectoderm buried in the naso-optic
furrow.
1
The membranous labyrinth (internal ear) is DEVELOPMENT OF THE EYE
derived from a thickening of surface ectoderm
The various components of the eyeball are derived
called the otic placode. T h e p l a c o d e is
converted into the otic vesicle and then to from the following primordia:
different parts of the labyrinth.
The bony labyrinth is formed from mesenchyme (a) An o u t g r o w t h from the prosencephalon
surrounding the membranous labyrinth. called the optic vesicle.
(b) A specialized area of surface ectoderm
The middle ear and auditory tube develop from (called the lens placode) that gives rise to
the tubotympanic recess (from first and second
the lens.
pharyngeal pouches).
(c) The mesoderm surrounding the optic vesicle.
T h e malleus a n d incus are derived from
Meckel's cartilage. The stapes is derived from
Formation of the Optic Vesicle
the cartilage of the second pharyngeal arch.
The external acoustic meatus is derived from 1. The region of the neural plate destined to
the first ectodermal cleft. The auricle is formed form the prosencephalon shows a linear
from swellings that appear around the cleft. thickened area on either side (Fig. 19.IB).
The Eye and Ear
Optic stalk
Optic vesicle
Cavity of prosencephalon
Fig. 19.3 Development of the lens vesicle and its invagination into the optic c u p .
Ciliary and
iridial
parts of
retina
posterior wall lose rheir nuclei a n d are retina, and also the supporting elements.
converted into the fibres of the lens. The The axons of the ganglion cells grow into
anterior layer remains as the epithelium the marginal layer to form the layer of nerve
covering this aspect of the lens. fibres. These fibres grow into the optic stalk
2. The retina is derived from the layers of the by passing through the choroidal fissure.
optic cup. The optic cup is divisible into: The optic stalk, is thus, converted into the
(a) a larger posterior part t h a t becomes optic nerve.
thick and forms the retina proper (optical The vitreous is believed to be derived partly
part of retina); and (b) an anterior part that from ectoderm and partly from mesoderm.
remains thin and forms an epithelial T h e e c t o d e r m a l c o m p o n e n t is derived,
covering for the ciliary body and iris (ciliary mainly, from the optic c u p but the lens
and iri dial parts of retina: Fig. 19.6B). vesicle m a y also c o n t r i b u t e to it. T h e
The outer wall of the posterior part of mesodermal component comes into the optic
the optic cup remains thin. Its cells form cup through the choroidal fissure.
the pigmented layer of the retina. The inner T h e choroid is formed from the inner
wall of the cup differentiates into matrix vascular layer of mesoderm that surrounds
cell, mantle and marginal layers as in the the optic cup (Figs 19.6A, 19.7). According
neural tube. After giving origin to the cells to some authorities this mesoderm contains
of the mantle layer, the cells of the matrix cells derived from the neural crest.
layer form the rods and cones. The cells of The mesodermal basis of the ciliary body
the mantle layer form the bipolar cells^ the a n d iris is d e r i v e d f r o m a f o r w a r d
ganglion cells and other neurons of the prolongation of the mesoderm forming the
Mesodermal part
of cornea
Anterior
chamber
Fig. 19.7A Derivation of coats of the eyeball. Note pupillary membrane and
hyaloid artery. For parts of retina, see Fig. 19.6.
The Eye and Ear
Fig. 19.7B The hyaloid artery and pupillary membrane have disappeared.
Position of artery can be seen as the hyaloid canal.
Human Embryology
We have seen already that this mesoderm forms the iridopupillary membrane. This membrane
the choroid and contributes to the ciliary body normally disappears before birth.
and iris. Part of this mesoderm, which gets
invaginated into the optic cup, forms the retinal Accessory Structures of Eyeball
vessels. The central artery and vein of the retina
at first lie in the choroidal fissure, but come to The eyelids are formed by reduplication of the
be buried in the fibres of the developing optic surface ectoderm above and below the cornea
nerve. As the choroidal fissure extends for some (Fig. 19.8). The ectodermal folds formed contain
distance along the optic stalk, the central artery some mesoderm that gives rise to muscle and to
of the retina runs through the substance of the the tarsal plates. As the folds enlarge, their margins
distal part of the optic nerve. approach each other. Ultimately, they meet and
Initially, the lens is completely surrounded fuse together. The lids thus cut off a space called
by a vascular capsule. The posterior part of the conjunctival sac. The conjunctiva is, thus, of
the capsule is supplied by the hyaloid artery ectodermal origin. The lids remain united with
(Fig. 19.7A). This artery is a continuation of each other until the seventh month of intrauterine
the central artery of the retina a n d passes life. (In many lower animals, e.g. cats, the offspring
through the vitreous. Later in fetal life, the are born with fused eyelids).
vascular capsule and the hyaloid artery The lacrimal gland is formed from a numher
disappear, but the hyaloid canal in the vitreous of b u d s t h a t arise from the u p p e r angle of
(through which the artery passes) persists. conjunctival sac (Fig. 19.8D).
The anterior part of the vascular capsule of The lacrimal sac and nasolacrimal duct are
the lens, comes to be lined posteriorly by the derived from the ectoderm of the naso-optic (or
iridial part of the retina a n d forms the iris nasolacrimal) furrow (Fig. 19.9). This furrow lies
(Fig. 19.7A, B). The pupil is for some time closed along the line of junction of the maxillary process
by a part of this vascular tissue, which is termed and the lateral nasal process, and extends from
The Eye and Ear
Surface %wFoldof
ectoderm ectoderm
Conjunctival
sac
Primitive
mouth'
Fig. 19.12 (A) Synophthalmos (fused median eye). A section through such an eye is shown in (C). In (B) w e
see synophthalmos, and a proboscis above the median eye.
Fig. 19.14 (A) Coloboma of upper l i d . (B) Epicanthic fold. Such , fold is normal in some races, e.g.
Mongolian (Chinese).
A Neural tube
(Metencephalon)
Semicircular ducts
Endolymphatic sac
Vestibular part
r\P
-Duct of cochlea
Fig. 19.17 Gradual transformation of a rounded otic vesicle to the highly complicated form of the
membranous labyrinth.
The Eye and Ear
Crista in
ampulla of
/ semicircular duct
Vestibular
ganglion *
(cM
\\-*f -'•
%
r _^S/ // Macula in
utricle
m* 1 m(&/*M /*W
• • ' \ ^ J / M
X l - • 'LAW
Fig. 19.18 Specialized sensory areas developing in the internal ear and their nerve supply.
Human Embryology
Mesenchymal^
condensation
Membranous _
labyrinth
Cartilage .
/ y^^^^vlr«
Labyrinth
f-fli^
V v"->;:>^ /
Loose
periotic
tissue
Semicircular duct
Semicircular canal
-Bone
Foramen vestibuli
Vestibule
T.S. of - ^
semicircular ^ /
canal — Foramen cochlea
Scala vestibuli
Scala tympani
Duct of cochlea
Fig. 19.20 Some parts of bony labyrinth (black), and of membranous labyrinth (pink).
The Eye and Ear
labyrinth. (Fig. 19.19A). This mesenchyme around the semicircular ducts also disappears
becomes condensed to form the otic capsule. The to form the semicircular canals. Two distinct
mesenchymal condensation is soon converted into spaces are formed, one on either side of the
cartilage. Between this cartilage and the cochlear duct. These are the scala tympani and
membranous labyrinth there is a layer of loose the scala vestibuli. The scala vestibuli
periotic tissue (Fig. 19.19B). The spaces of the bony communicates with the vestibule while the
labyrinth are created by the disappearance of this scala tympani grows towards the tympanic
periotic tissue. The membranous labyrinth is filled cavity, from which it remains separated by a
with a fluid called endolymph, while the periotic membrane (Fig. 19.20). The cartilaginous
spaces surrounding it are filled with perilymph. labyrinth is subsequently ossified to form the
bony labyrinth (Fig. 19.19D).
Otic capsule
a
1st pouch ^s-^
' i
s>
Tubo-tympanic recess
2nd pouch
^^•^s01
Tympanum
Pharyngo-tymapanic tube
Fig. 19.21 Development of the middle ear (tympanum). Formation of tubo-tympanic recess(A), and its
subdivision into the tympanum and the pharyngo-tympanic tube (B).
Otic capsule x
Cartilage of 1 st arch
Cartilage of 2nd
Fig. 19.22 The ossicles of the middle ear develop from the first and second pharyngeal arches.
Human Embryology
Tympanum
Stapes
y Incus
# y Malleus — External
acoustic
meatus
Tubo-tympanic
recess
Tubo-tympanic recess
Layers ot tympanic membrane -
f " 1st
ectodermal Endoderm (inner)
Mesoderm
(middle)
^ T \ / Ectoderm (outer)
I
Solid proliferation |
of cells of cleft
External
acoustic meatus
Fig. 19.24 Development of external acoustic meatus. Fig. 19.25 Layers of tympanic membrane.
The solid mass of ectodermal cells seen in
(B) has been canalized in (C).
pharyngo-tympanic tube is derived from the tubo- mucous membrane, which covers them throughout
tympanic recess. This recess develops from the life (Fig. 19.23). The ossicles of the ear fully ossify
dorsal part of the first pharyngeal pouch, and also in the fourth month of intrauterine life. They are
receives a contribution from the second pouch (Fig. the first bones in the body to do so.
19.21). The tympanic antrum and mastoid air cells The tensor tympani is derived from the
are formed by extensions from the middle ear. mesoderm of the first pharyngeal arch and the
The malleus and incus are derived from the stapedius from that of the second arch.
dorsal end of Meckel's cartilage, while the stapes
is formed from the dorsal end of the cartilage of
the second pharyngeal arch (Fig. 19.22). The External Ear
ossicles are at first outside the mucous membrane The external acoustic meatus is derived from the
of the developing middle ear. They invaginate the dorsal part of the first ectodermal cleft
The Eye and Ear
First
Vyy ectodermal cleft
Fig. 19.26 Development of the auricle. (A) First ectodermal cleft around which the auricle develops. (B) Small
swellings or hillocks appear. (C) Hillocks gradually fuse with one another to form the auricle.
(Fig. 19.24A). However, its deeper part is formed its layers, because of upward extension of
by proliferation of its lining epithelium, which the membrane.
grows towards the middle ear (Fig. 19.24B). This
proliferation is at first solid {meatal plug), but is Anomalies of the Ear
later canalized (Fig. 19.24C).
The auricle, or pinna, is formed from about six Anomalies of the Auricle
m e s o d e r m a l t h i c k e n i n g s (called tubercles or 1. The development of the auricle may get
hillocks) that appear on the mandibular and hyoid arrested at any stage. As a result of this, it
arches, around the opening of the dorsal part of may be totally, or partially, absent; it may
the first ectodermal cleft (i.e. around the opening be represented by isolated nodules; or it
of the external acoustic meatus) (Fig. 19.26). may be very small. Alternatively it may
be very large.
The mandibular arch forms only the tragus and 2. T h e m i g r a t i o n of the auricle from its
a small area around it, the rest of the auricle primitive c a u d o - v e n t r a l position may
being formed from the hyoid arch. This is remain incomplete. We have seen that this
consistent with the fact t h a t the a u r i c u l a r migration occurs as a result of the growth
muscles are supplied by the facial nerve. of the maxillary and m a n d i b u l a r p r o -
cesses. This explains the association of
Tympanic M e m b r a n e c a u d o - v e n t r a l d i s p l a c e m e n t of t h e
auricle with mandibulofacial dysostosis.
This is formed by apposition of the tubo-tympanic
recess and the first ectodermal cleft, these t w o
Anomalies of the External
forming the inner (endodermal) and outer
Auditory Meatus
(ectodermal) epithelial linings of the membrane.
The intervening mesoderm forms the connective
tissue basis (Fig. 19.25). 1. There may be stenosis, or atresia, of the
meatus over its whole length or over part
of it. T h e lumen may be closed by fibrous
Two points worth noting are as follows:
tissue, by cartilage, or by bone.
1. The handle of the malleus grows into the 2. The normal curvature of the meatus may
connective tissue from above. be accentuated as a result of which the
2. The chorda tympani nerve is at first outside tympanic membrane cannot be fully seen
the membrane but later comes to lie within from the outside.
Human Embryology
DERIVATIVES OF ECTODERM
Lining Epithelia
The epithelium lining the following is of
ectodermal origin:
8. Testis, epidydimis, ductus deferens, seminal 10. Lining mesothelium of bursae and joints.
vesicle, ejaculatory duct. 11. Substance of cornea; sclera; choroid. (?)
9. Lining mesothelium of pleural, pericardial 12. Substance of ciliary body and iris.
and peritoneal cavities; and of tunica 13. Duramater; pia-arachnoid (?); microglia.
vaginalis. 14. Adrenal cortex.
Chapter
Table 21.1 Age of human embryo as indicated by C.R. length and appearance of pairs of somites
Two ova may be shed simultaneously from develop independently. In such a case,
the ovary. Each of them may be fertilized the fetuses will have separate chorionic
and may develop in the usual manner. This and amniotic sacs, as in dizygotic twins.
results in twins that are called dizygotic or (b) The embryo may develop normally up
fraternal twins. As each of them develops to the stage of the morula. However,
from a s e p a r a t e o v u m a n d a s e p a r a t e when the blastocyst is formed, two inner
s p e r m a t o z o o n , they h a v e i n d e p e n d e n t cell masses form within it and each
genetic constitutions. These twins, therefore, develops into a c o m p l e t e fetus. In
need not be of the same sex, nor do they this case the t w o fetuses have a
resemble each other any more than children common chorionic sac but each lies in
of the same parents that are born separately. an i n d e p e n d e n t a m n i o t i c cavity
E a c h fetus h a s its o w n c h o r i o n i c a n d (Fig. 21.2B).
amniotic sacs (Fig. 21.2A), (c) Lastly, the inner cell mass may split
Twins can also arise from a single fertilized into t w o ; or two embryonic axes may
o v u m . These are called monozygotic or be established in one inner cell mass.
maternal twins. The genetic constitution of By this we mean t h a t t w o separate
the two twins is exactly the same. Hence embryonic discs are formed within it,
they are of the same sex. They are also each with its own prochordal plate and
exactly alike in appearance. primitive streak. In this case the two
Monozygotic twins are produced in one fetuses share a c o m m o n c h o r i o n as
of the following ways: well as a c o m m o n a m n i o t i c cavity
(Fig.21.2C).
(a) The cells formed in the first few divisions
of the zygote are totipotent, i.e. each In those instances where the retuses share a
cell is capable of developing into a common chorion, there is one placenta to which
complete embryo. The two cells formed t w o umbilical c o r d s are a t t a c h e d . W h e r e the
by the first division may separate and chorionic sacs are s e p a r a t e , t w o independent
Fig. 21.2 (A) Dizygotic twins. Each twin has its own chorion and amnion. (B) and (C) Monozygotic twins.
The chorion is common. The amnion can be common or separate.
Human Embryology
placentae are formed. Such placentae may Multiple births may occur by subdivision of
secondarily fuse with each other, but normally one zygote into more than two parts, by the
there are no anastomoses between the vessels of simultaneous fertilization of more than two ova,
the two placentae. Rarely, the placentae can fuse or by a combination of both these factors
and there may be mixing of blood of the two fetuses. (Figs 21.3, 21.4).
In that case the blood of each fetus may contain Incomplete separation of monozygotic twins
two types of erythrocytes. The condition is known results in the birth of two infants that are joined
as erythrocyte mosaicism. together in some part of the body. In some cases,
A
GD
/x
t tl
1 Fig. 21.3 2Derivation
3 of triplets (A) from one ovum; and (B) from two ova.
Fig. 21.4 Two ways in which quadruplets may be derived from two ova.
Some General Considerations
it is possible to separate them by operation, but other fetus for its blood supply. Sometimes, it may
most of them are born dead. These are called be represented by just a mass attached to the other
conjoined twins or Siamese twins. fetus, or may even be embedded within its body.
Not infrequently the two twins do not undergo The incidence of twinning differs in different
equal development, possibly as a result of unequal races and in different countries. Twins occur in
blood supply. The underdeveloped fetus may pos- one to two per cent of pregnancies and about 70
sess no heart of its own and may depend upon the per cent of them are dizygotic.
Chapter
differentiated cell possesses new morphological substances, which are probably complex
and functional characteristics, which distinguish proteins, including enzymes.
it from o t h e r cells. We n o w k n o w t h a t these 4. The chemical substances elaborated by the
characteristics result from the formation of new organizer may be:
enzymes and proteins. Earlier workers tried to
(a) inductors which stimulate the tissue to
s t u d y t h e m e c h a n i s m of d i f f e r e n t i a t i o n by
differentiate in a particular manner;
experiments on embryos of amphibia and chicks.
or
Their work has produced many interesting results
some of which are as follows: (b) inhibitors which have a restraining
influence tin differentiation.
1. It has been observed that certain regions of These observations recorded were empirical.
the embryo have the ability to influence the With the advent of molecular biology we know
differentiation of neighbouring regions. One that the production of organizers, inductors and
of the most interesting instances of this inhibitors are controlled by genes. In other words
phenomenon is the influence exerted by the we can say that development is controlled by
optic vesicle on the overlying skin to form genes. A study of the controlling mechanisms can
the lens vesicle. It has been shown that the be termed Genetic control of development. It can
lens vesicle fails to form if the optic vesicle a l s o d e s c r i b e d as Molecular control of
is removed. Conversely, if the optic vesicle development.
is transplanted elsewhere (e.g. under the
Genes exert their influence on cellular functions
skin of the abdomen) the overlying skin
by synthesis of proteins. The proteins synthesized
there begins to form a lens vesicle. These
differ from cell to cell and even within the same
experiments show that the optic vesicle
cell, at different times. This provides the basic
induces the formation of the lens vesicle.
mechanism for control of any process, including
The influence exerted by such an area (i.e.
embryonic development.
optic vesicle) is called induction whereas
Recent researches have provided us with a vast
the area exerting the influence is called an
amount of information about individual genes and
organizer.
about the various factors produced by them to
2. The first organizer that is recognizable in control developmental processes step by step. A
the embryo is the dorsal lip of the blastopore, detailed study of these is beyond the scope of
which is, therefore, called the primary medical s t u d e n t s . It belongs to the fields of
organizer. Removal of this region results in molecular biology and of genetics. The account
total failure of embryonic development. that follows seeks to give students some idea of
However, on the other hand if the dorsal the subject without confusing them with too many
lip of the blastopore is grafted on to an unfamiliar terms and concepts.
ectopic site of another embryo, it induces
As you know all information in cells is stored
the development of an entire embryo. This
in molecules of D N A . To u n d e r s t a n d genetic
indicates that signals for the development
processes we have to first know some facts about
of the e m b r y o have originated from the
D N A structure.
d o r s a l lip a n d h a v e i n f l u e n c e d t h e
differentiation of surrounding tissues.
SOME FEATURES OF DNA STRUCTURE
Organizers that appear later in develop-
ment have correspondingly lesser effects. DNA in a chromosome is in the form of verv fine
3. It is n o w known that the organizers exert fibres. Each fibre consists of t w o strands that are
their influence by e l a b o r a t i n g chemical twisted spirally to form what is called a double
Human Embryology
helix. The two strands are linked to each other at chain (Fig. 22.2). The nitrogenous base is
regular intervals. a t t a c h e d to the s u g a r m o l e c u l e a n d is
directed at right angles to the long axis of
1. Each strand of the D N A fibre consists of a the polynucleotide chain.
chain of nucleotides. Each polynucleotide chain has marked ends.
2. Each nucleotide molecule is made up of one In Fig. 22.2, at the upper end the 5th carbon
molecule of sugar (deoxyribose), a molecule atom of the sugar molecule is not linked to
of p h o s p h a t e a n d a n i t r o g e n o u s b a s e any other nucleotide. This end is called the
(Fig. 22.1). As there are four nitrogenous 5' or 5' P terminus. The other end of the
b a s e s (adenine, guanine, cytosine or chain ends in a sugar molecule whose 3rd
thymine) there are four types of nucleotide. carbon a t o m is n o t linked t o any other
3. In a nucleotide the phosphate molecule is nucleotide and bears an 3'-OH group. This
attached to fifth carbon atom of the sugar end of the polynucleotide chain is called
(deoxyribose) and the nitrogenous base is the 3 ' end or 3 ' O H terminus.
attached to first carbon atom. The DNA molecule is made up of two such
4. The phosphate molecule of a nucleotide is polynucleotide chains which lie side by side
joined to the third c a r b o n a t o m of the but run in opposite directions (antiparallel).
deoxyrihose of the next nucleotide. Thus the
sugar and phosphate molecules are arranged
in a linear fashion to form a polynucleotide
Fig. 22.3 Antiparallel polynucleotide chains showing sugar-phosphate backbone and nitrogenous base
pairing. The nitrogenous base Cytosine (C) always pairs w i t h Guanine (G) w h i l e Adenine (A) pairs
w i t h Thymine (T). (A) Schematic diagram. (B) Structural diagram.
One chain runs in the 5'-3' direction, the strands of DNA are complementary to each
other in the 3'-5'direction (Fig. 22.3). other. If the sequence of bases on one chain
7. T h e t w o c h a i n s a r e h e l d t o g e t h e r by is ATGCA then the corresponding region on
hydrogen bonds between the nitrogenous other chain will have the sequence TACGT.
bases (Fig. 22.3). 10. Two complementary chains (polynucleotide
8. The pairing between nitrogenous bases is chains) of DNA are twisted around each
fixed, i.e. adenine (A) always pairs with other to form w h a t is called double helix.
thymine (T), and cytosine {C} with guanine
(G). The specific pairing is due to the fact Every protein is made up of polypeptide chains,
that their molecules are complementary and which in turn are made up of series of amino acids.
perfect hydrogen bonds are formed easily. The nature of the protein depends upon the amino
A and T share two hydrogen atoms while C acids present and the sequence in which they are
and G are joined by three hydrogen bonds. arranged. A sequence of three bases on a DNA
9. As there is specific base pairing, the two s t r a n d , codes for one a m i n o acid. Under the
Human Embryology
influence of D N A , these amino acids are linked A structural gene not only contains the sequence
together in a particular sequence to form proteins. of e x o n s a n d i n t r o n s b u t a l s o p o s s e s s e s
Thus the order in which these bases are arranged flanking r e g i o n s at its e n d s . T h e s e flanking
along the length of a strand of D N A determines regions are i m p o r t a n t for regulation of gene
the nature of the protein that can be synthesized. expression (Fig. 22.4). At the 5 ' end the flanking
region is m a d e u p of D N A sequences, w h i c h
controls transcription. This region is called the
MOLECULAR STRUCTURE OF A GENE
promotor region. It contains a 'TATA' box which
Chemically, a gene is composed of DNA. In simple is essential for t r a n s c r i p t i o n . F o l l o w i n g the
language a structural gene can be defined as l a promotor region there is a code for initiation of
segment of DNA which contains the information transcription, which is followed by the code for
(code) for the synthesis of one complete polypeptide initiation of translation (ATG). At the 3' end the
chain (or an enzyme)'. Thus a gene is nothing but f l a n k i n g r e g i o n c o n s i s t s of a t r a n s l a t i o n
a set of instructions for making proteins. termination codon (TAA), which is followed by a
As each polypeptide chain is made of sequential poly (A) cap codon.
a r r a n g e m e n t of specific a m i n o acids, it w a s For initiation of transcription, it is necessary
expected that there would be a contiguous sequence that the p r o m o t o r region should bind to RNA
of D N A c o d i n g for these a m i n o acids (in a polymerase. However, in order ro hind to rhis site
structural gene). However, it is now k n o w n that the polymerase requires additional proteins called
many non-coding sequences, called introns arc transcription factors. Transcription factors acting
interposed between the coding sequences or exons. in c o m b i n a t i o n with o t h e r p r o t e i n s activate
The number of introns in various genes is variable D N A t r a n s c r i p t i o n (gene e x p r e s s i o n ) . D N A
and sometimes it may so happen that introns are transcription starts at the 5 ' end and ends at
much larger than exons (coding sequences). During the 3' end of a gene. The flanking region of
t r a n s c r i p t i o n , both exons and introns are the 3 ' end helps in the stabilization of newly
t r a n s c r i b e d hut i n t r o n s are n o t included in formed m R N A and allows it to go out of the
mature RNA. nucleus.
Transcription Transcription
Intron
initiation termination
I Enhancer
sequence
Translation
termination
Poly A addition site
Transcription
termination
Intron
Transcription
stops
Primary mRNA
Mature mRNA
•
Fig. 22.5 Transcription of mRNA from DNA (A). 5' capping and 3' end polyadenylation (B), and splicing of
mRNA to get mature RNA (C).
Human Embryology
together to form mature RNA. It is obvious constitute polypeptide chains. Proteins are
that mature RNA does not have any introns formed by union of polypeptide chains.
and is therefore shorter. This process of 5. The flow of information from DNA to RNA
removal of introns (by cutting them off and and finally to protein has been described as
joining the ends of extrons) is k n o w n as the 'central dogma of molecular biology'.
splicing.
• A molecule of methylguanine gets attached SOME FURTHER DETAILS ABOUT
to the 5' end. It is called the methylguanine GENES AND PROTEIN SYNTHESIS
cap. This 5 ' cap protects m R N A from
d e g r a d a t i o n and facilitates t r a n s p o r t of (a) At one time it was taught that one gene
m R N A to cytoplasm. Similarly, the 3 ' end p r o d u c e d only one p r o t e i n or e n z y m e .
of m R N A bears a poly (A) tail, which also However, it is now k n o w n that although
p r o t e c t s m R N A from d e g r a d a t i o n a n d there are only about 35,000 genes in the
f a c i l i t a t e s the t r a n s p o r t of m R N A t o human genome, proteins number more than
cytoplasm. 100,000. The mechanism by which a single
• The m R N A then migrates from nucleus to gene can give rise to many proteins is as
cytoplasm where it attaches to ribosomes follows.
for synthesis of protein (translation). As s t a t e d earlier, a single gene can
synthesize more than one protein. This is
Translation achieved by the process called alternative
splicing. In this process, the exons are
1. As stated in the preceding section, in the spliced in different patterns (Fig. 22.6). The
cytoplasm, messenger RNA becomes absence of one or t w o exons in m R N A
attached to a ribosome. changes the sequence of amino acids present
2. The cytoplasm also contains another form in the resulting polypeptide chain. In this
of RNA called transfer RNA. O n one side way different proteins are formed.
transfer RNA becomes attached to an amino Similarly, the function of the protein, made
acid. On the other side it bears a code of from the mRNA, can also be modified by
t h r e e b a s e s {anticodon) that are its phosphorylation, or by its combination
complementary to the bases coding for its with other proteins. This explains why the
amino acid on messenger RNA. Under the number of proteins exceeds by almost three
influence of the ribosome several units of times the number of genes present in the
transfer RNA, along with their amino acids, human genome.
become arranged alongside the strand of (b) A n o t h e r i m p o r t a n t fact a b o u t g e n e
messenger RNA in the sequence determined regulation of development is that cells of
by t h e c o d e on m e s s e n g e r R N A . T h i s one type differ from those of other types
process is called translation. because they synthesize different proteins,
3. The amino acids now become linked to each including enzymes. However, we have also
other to form a polypeptide chain. Now, it seen that each cell of the body (except a
will be clear that the amino acids are linked germ cell) has exactly the same complement
up exactly in the order in which their codes of genetic material (in the form of DNA) as
are arranged on messenger RNA, which in the fertilized o v u m . H o w is it then t h a t
t u r n is based on the code on the D N A different cell types come to produce different
molecule. types of protein, i.e. skin cells produce
4. Chains of amino acids formed in this way k e r a t i n , t h o s e of e n d o c r i n e p a n c r e a s
Molecular Control of Development
Exons Introns
/ \ / \
Three varieties
of mRNA formed
by alternative
splicing
Fig. 22.6 Diagram showing the process of alternative splicing. Transcription of a structural gene may form a
mature mRNA in which all exons are present (A); where one exon is excluded in the process of
splicing (B and C). Thus a single gene can form three different kinds of proteins.
synthesize insulin and red blood cells or for the control of the process in other
produce haemoglobin, etc.? ways. The DNA sequence that provides the
The answer ro this question lies in the signal for initiation of transcription is called
concept that in any given cell only a few of the promoter. Binding of RNA polymerase
irs genes are active and others are resting. to the promoter causes the DNA fibre to
A gene that is active is said to be expressed. uncoil and thus makes it possible for RNA
Differentiation of cells takes place because polymerase to reach the fibre and to begin
of the expression of a small number of deve- the process of transcription. However, to
lopmental regulatory genes (mastergenes) bind to the promoter region the RNA
acting at specific times of development. polymerase also needs a transcription factor.
(c) Every differentiated cell contains two types Transcription factors (gene regulatory
of genes, i.e. house keeping genes and proteins) are present in the nucleus. They
specialty genes. The majority of genes determine the region of the DNA to be
(80-90%) in a cell are house keeping genes transcribed. Transcription continues up to
which are required for basic cellular the region of the DNA fibre that bears a
metabolic functions. These genes are code that gives a signal for termination of
common to different cell types. The transcription.
speciality genes are expressed to define the (e) Apart from initiating the process of
unique features of different cell types. transcription, the promoter also determines
the rate of transcription. DNA sequences,
(d) In addition to the protein coding sequences
which increase the rate of transcription are
(of bases) DNA also bears other regions that
called enhancers, while regions that inhibit
have a controlling function. These regions
transcription are called silencers (or
provide signals for initiation and
repressors).
termination of the process of transcription,
Human Embryology
The enhancers and silencers can reside 3. Activation of signal transducing proteins
anywhere along the DNA strand of a gene. within the cell cytoplasm.
The transcription factor not only binds to 4. Activation of transcription factor, which
the promoter region of a gene but also binds binds to D N A in the nucleus and finally
and activates the enhancer region, which leads to transcription. In other words the
regulates the timing of gene expression in a gene is now expressed.
specific cell. A single gene m a y h a v e
separate enhancers in different tissues. Thus
Growth and Differentiation Factors
the same gene is expressed at different time
in various tissues during development, i.e. T h e term growth factor refers to a naturally
in some tissues it is expressed earlier, in some occurring protein capable of stimulating cellular
later. proliferation and cellular differentiation. Growth
factors are important for regulating a variety of
cellular processes. These factors are different for
ROLE OF GROWTH AND different cells. The epidermal growth factor (EGF)
DIFFERENTIATION FACTORS, stimulates epidermal cells; the fibroblast growth
GROWTH FACTOR RECEPTORS, factor (FGF) stimulates fibroblasts; and the platelet
PROTEIN KINASE AND derived g r o w t h factor {PDGF) stimulates the
TRANSCRIPTION FACTORS IN proliferation of connective tissues.
GROWTH AND DEVELOPMENT
G r o w t h factors typically act as signalling
At present it is well known that several genes and molecules among cells in embryos. Examples are
g e n e f a m i l i e s p l a y i m p o r t a n t r o l e s in t h e cytokines and h o r m o n e s t h a t bind to specific
development of the embryo. Most of these genes receptors on the surfaces of their target cells. As
produce transcription factors (described above), described above, cell-to-cell signalling is necessary
which control RNA transcription. Transcription for induction of cellular differentiation. Signals in
factors play an important role in gene expression the form of growth and differentiation factors are
as they can switch genes on and off by activating transmitted from one cell to another by endocrine,
or repressing t h e m . It is believed t h a t m a n y paracrine or juxtacrine interactions.
transcription factors control many other genes,
• Endocrine signals: These signals are
which regulate fundamental embryological
hormones, which travel through the blood
processes like induction, segmentation, migration,
to reach distant places in the body.
differentiation and apoptosis (programmed cell
death). These fundamental embryological • Paracrine signals: These signals target cells,
p r o c e s s e s a r e m e d i a t e d by g r o w t h a n d which are present in the neighbourhood of
differentiation factors, growth factor receptors and the emitting cell.
various cytoplasmic proteins. • Juxtacrine signals: In this kind of signalling
it is necessary that adjacent cells should be
Several c o m p o n e n t s are r e q u i r e d for t h e
in cell-to-cell physical contact. Well-known
expression of a given gene. These are:
e x a m p l e s of t h e s e are signals p a s s i n g
through 'gap junctions' and 'notch
1. Growth factors, which act as cell signalling signalling' (described later in this chapter).
m o l e c u l e s for i n d u c t i o n of c e l l u l a r
differentiation. Some c o m m o n g r o w t h and differentiation
2. Receptors, which are present in the cell factors are given in Table 2 2 . 1 . This information
membrane. Their function is to recognize is for reference only. It does n o t have to be
and respond to growth factors. remembered.
Molecular Control of Development
Bone Morphogenetic Factors (BMP 1 to 9) Bone formation, cell division, cell migration and
apoptosis.
6. Insulin-like G r o w t h Factors (IGFs) IGF-1 acts as a factor for bone growth, IGF-2 is a
fetal growth factor.
Complex acts as
transcription factor
of inhibitory gene
Fig. 22.7 Diagram showing Delta-Notch pathway. In this kind of signalling the Notch receptor of a
neighbouring cell binds to Delta protein present on a dominant cell. This leads to cleavage of
intracellular part of the Notch receptor, which forms a Deltex complex and enters the nucleus. In
the nucleus this complex acts as a transcription factor of a gene whose products repress the
expression of many other genes which are required for the promotion of differentiation. This
ultimately prevents the cell from differentiating into the dominant cell type.
One cell
becomes
dominant.
0®®
-°M> 1
' h^Q)
Dominant cell Ci) t
similar cells sends inhibitory Others become
signals. neuroglial cells.
Fig. 22.8 Diagram showing the process of lateral inhibition. O u t of a group of d e v e l o p m e n t a l ^ similar cells
one cell changes to a dominant type (e.g. neuron). W h a t leads to its differentiation as a dominant
cell is not k n o w n . The dominant cell gives off inhibitory signals to neighbouring cells through the
notch signalling pathway. The dominant cell differentiates into a neuron w h i l e neighbouring cells
develop into neuroglial cells.
« When a growth factor binds to its specific which encodes for a transcription factor. The
receptor, it leads to the activation of mutation of this gene causes abnormalities of
receptor. the eye.
• The activated receptor in turn activates a
series of proteins. These proteins are called Transcription Factors
signal transducing proteins. Many such
proteins are present on inner surface of the Transcription factors regulate gene expression by
plasma membrane. acting on promoter or enhancer regions of specific
• The active signal transducing protein of the genes. A large number of transcription factors are
cell membrane in turn activates cytoplasmic common and found in all types of cells. However,
proteins (kinases). Thus a cascade of protein some transcription factors are found only in certain
activation is established. types of cells or are active only during some stages
• This ultimately activates a transcription of development. Some transcription factor genes
factor. are given in Table 22.2.
• The transcription factor then binds to DNA
in the nucleus and activates or inhibits the CLINICAL CORRELATION
expression of the growth and differentiation Abnormalities in the growth factor signalling
related gene. pathway may lead to abnormal growth or
cancer. The over-expression of growth factors
In the beginning of this chapter we have seen can lead to a non-cancerous disorder like
that the formation of the lens is induced by the psoriasis. Mutation and over-expression of the
optic vesicle, i.e. the optic vesicle transmits a PDCF gene may also cause cancers, i.e.
molecular signal to the lens placode. After receiving osteosarcoma and astrocytoma.
this signal, the cells of the optic placode initiate a Mutation in growth factor receptors can lead
program of gene expression leading to the to insulin-resistant diabetes (insulin receptor)
differentiation of lens vesicle to lens. Now, we and dwarfism (fibroblast growth factor
know that the development of the eye is receptor). Mutation and over-expression of these
under the control of a specific gene (PAX-6), receptors are responsible for a variety of cancers
Human Embryology
o
0- Nuclear membrane
Fig. 22.9 In a normal cell when a growth factor binds to a growth factor receptor, it gets stimulated. The
inactive transducing protein gets activated and sends a signal to the nucleus by activating a series
of cytoplasmic kinases. The signal reaching the nucleus in the form of a transcription factor
begins transcription of the gene.
2. Zinc Finger Protein ( W T - 1 , GLI3, 2 I C 2 , ZIC3) Regulates the formation of kidney and gonads.
4. PAX Genes (paired genes) Sense organs (eye and ear) and nervous system
(PAX-1 to PAX-9) development, cellular differentiation at the time of
epithelial mesenchymal transition.
and thorax. The posterior end of a Drosophilia genes called zygotic genes. The zygotic genes start
embryo (abdominal segments) is determined by expressing after superseding 'maternal effect genes'.
nanos class of gene. A t h i r d g r o u p of genes The segmentation of the oval-shaped embryo of
determines the most anterior (acron) and most Drosophila is completed in three steps.
posterior (telson) structures. The most important T h e first step of segmentation is under the
gene of this group is named torso. The dorsoventral c o n t r o l of gap genes (Hunchback, Kruppel,
axis of the embryo is determined by a separate set orthodenticle, tailless, etc.), which divide the
of genes. The main gene for this axis is named embryo into broad regions. The second step is
dorsal. under the control of pair rule genes (Hairy, runt,
In contrast to Drosophila, where body axes are odd, paired, odd skipped and even skipped, etc.),
established even before fertilization, in mammalian which subdivide the embryo into 7 segments along
embryos body axes do not become fixed until the the cranio-caudal axis (Fig. 22.10). The third step
e n d of c l e a v a g e or e a r l y g a s t r u l a t i o n . T h e in segmentation is governed by segment polarity
molecular control of formation of the embryo (till genes (Gooseberry, engrailed, hedgehog, patched,
the formation of bi-layer germ
disc or before gastrulation) is
Dorsal
not fully u n d e r s t o o d . In the Head region Tail region
human embryo the formation
of an antero-posterior axis is Broad regions
signalled by the cells of the determined by
future anterior margin of the Gap genes
embryonic disc. This area of the
disc expresses the genes (OTX2,
LIM1 and HESX1), which are
necessary for formation of the
head. This is soon followed by
f o r m a t i o n of t h e p r i m i t i v e
streak under the influence of Seven segments
B-Catenin, BMP-4 and activin, determined by
pair rule genes
which are first expressed in the
cranial region of the embryo.
O n c e the primitive streak is
formed the e m b r y o n i c a x e s
(cranio-caudal, dorso-ventral
and right/left) are well
established. 14 segments
determined by
segment polarity genes
Segmentation
The next step in the
development of Drosophila is Fig. 22.10 The process of establishment of the axes in a Drosophila
the division of the embryo into embryo is governed by maternal effect genes. The
segmentation of the embryo is controlled by segmentation
i d e n t i c a l s e g m e n t s . T h i s is
genes (zygotic genes). Broad regions are determined by gap
a c h i e v e d by segmentation
genes (A), seven segments by 'pair rule genes' (B) and (C) 14
genes, which are a subclass of
segments by 'segment polarity genes'.
Molecular Control of Development
3' 5'
lab
)
pb
"ZP\
r T\t\ t^^^~^^~^
<-1
^ ^ dfb ^^tp abdB
5cr
abd A
• • ant ubx ^ ^ •
Antennapedia Bithorax genes
genes
Fig. 22.11 Diagram showing the arrangement of homeobox genes of Drosophila on chromosome number 3.
These eight genes are arranged in two clusters - Antennapedia and Bithorax. These genes are
expressed in a cranio-caudal sequence.
wingless, etc.), which divide the embryo into 14 brought about by the expression of a group of
segments. These genes govern differentiation bomeotic genes. These genes determine which
within segments. Out of these 14 segments, the embryonic segment should bear antennae, wings
first three ( C 1 - C 3 ) differentiate into the head or legs. These H homeotic genes are situated on
region; segments T 1 - T 3 become thoracic chromosome number 3 and are arranged in two
segments, a n d A 1 - A 8 give rise to a b d o m i n a l groups {Antennapedia and Bithorax) (Fig. 22.11).
segments. These genes are collectively called the homeotic
At present similar segmentation genes have also complex or HOM-C. All 8 genes contain a highly-
been identified in mammals. Now, we know that conserved 180 base pair region of DNA called the
segmentation of hindbrain, pharyngeal arches and homeobox. The h o m e o b o x encodes bomeodo-
of somites under the control of genes. mains of 60 amino acids. These homeodomains
recognize and bind to specific DNA sequences of
other genes.
determination ot Region
Characteristics T h e genes present in the homeotic complex
express themselves in a specific sequence. Genes
Once the segmentation of the embryo is completed, that are located at the 3' end of the D N A are
it is followed by imparting specific or regional expressed first a n d are meant for more cranial
characteristics to the newly formed segments. The structures of embryo. Genes present at the 5' end
r e g i o n a l m o r p h o g e n e t i c c h a r a c t e r i z a t i o n of are expressed later and are meant for caudal
individual segment of the Drosophila embryo is structures.
Human Embryology
The mutation of the antennapedia homeotic within the cluster, have the same functions as
gene results in formation of a leg instead of observed in Drosophila. The amino acid sequences
antennae. Similarly, mutation of the Ultrabithomx of homeodomains of Drosophila are up to 90 per
gene causes the third thoracic segment to develop cent similar to that of the human. During hundreds
as an additional second segment. Because of millions of years of evolution, these genes have
of this, four wings are formed instead of the normal duplicated twice so that humans have four copies
two. of homeobox containing genes {HOXA, HOXB,
These homeotic genes of Drosophila have been HOXC, and HOXD) arranged on four different
well conserved during evolution and are present chromosomes (Chromosome number 7, 17, 12
in humans and other mammals. The human genes and 2). Genes in each group are numbered from 1
(called HOX genes) have the same clustered to 13 (Fig. 22.12). Genes with same number but
organization, follow rhe same order of arrangement present on different chromosomes form a
Chromosome 7
—EH-5
Chromosome 17
EH~
HOXC Chromosome 12
[5]—Eg—|c5]- ^ - O—[l°l—[l]}—mi—m-
HOXD Chromosome 2
Fig. 22.12 Alignment of four human HOX complexes. Expression of paralogous groups in the hindbrain
and spinal cord, in cranial to caudal direction, are indicated by their numbers.
Molecular Control of Development
the cranio-caudal axis of the primitive streak is the left and right side of the embryo. Soon after its
genetically controlled. This is achieved by the a p p e a r a n c e , the n o d e a n d streak express the
e x p r e s s i o n of a g e n e c a l l e d Cripto, a gene fibroblast growth factor 8 [FGF-8), which induces
belonging to EGF family of growth factors. The the expression of the nodal gene on the left side of
organization of the head region is under the control the disc. After the induction of the neural tube the
of gene Lim-1. The k n o c k o u t of gene Lim 1 FGF-8 gene induces the nodal and Lefty 2 genes
produces an animal without a head. Other genes, in the lateral plate mesoderm on left side only
which help in the formation of the head region (Fig. 2 2 . 1 3 ) . T h e s e genes t h e n r e g u l a t e the
are Otx-1 and Otx-2 along with HNF-3 (hepato e x p r e s s i o n of PITX2, which is a h o m e o b o x
nuclear factors). The expression of the nodal gene c o n t a i n i n g transcription factor i m p o r t a n t for
of the TGF family is also necessary for the establishing left sidedness. The sonic hedgehox
d e v e l o p m e n t of cranial structures. T h e t r u n k (SHH) gene, which is expressed in the notochord,
organizing centre controls the development of prevents the expression of left sided genes on the
paraxial and lateral plate mesoderm of neck, the right side by acting as a barrier in midline. The
thorax and the abdomen. The formation of trunk e x p r e s s i o n of t h e snail gene o n r i g h t side
paraxial mesoderm is under the control of T-box establishes right sidedness. Because of h a n d e d
genes (Tbx-6 and brachyury). The fibroblast asymmetry, some organs in the body lie on the
growth factor-9 (FGF-9) appears to play a role in right side and some on left side (stomach, heart,
the formation of intermediate mesoderm. The tail spleen on the left side and the liver on the right).
organizing centre forms the mesoderm of the sacral After gastrulation, the development of various
r e g i o n . G e n e s r e s p o n s i b l e for f o r m a t i o n of systems of the body begin in the embryo. The
mesoderm of this region and caudal portion of d e v e l o p m e n t of e a c h s y s t e m is g e n e t i c a l l y
neural tube are brachyury, Wnt-Sa and WntSb. d e t e r m i n e d . For detailed i n f o r m a t i o n on the
T h e m u t a t i o n of Brachyury is responsible for molecular regulation of the development of each
caudal dysplasia or caudal dysgenesis. system students should consult books on genetics
The appearance of the primitive streak defines and a more detailed book on embryology.
Achondroplasia, 91, 125 Antigen, 326
Acrocephaly, 122 Antrum, tympanic, 110
Acrosomal reaction, 35 Aorta
Acrosome, 10 arch of, 211
Adenine, 332 double, 215
Adrenal, 300 interrupted, 216
Aglossia, 146 right, 215
Agnathia, 133 ascending, 211
Albinism, 101 coarctation of, 216
Alimentary system, 148 descending, 211
Allantoic diverticulum, 54 dorsal, 106, 210
Alopecia, 102 pharyngeal arch, 210
Amastia, 103 primitive, 210
Amelia, 125 ventral, 106, 210
Ameloblast, 140 Aortic sac, 210
Amniochorionic membrane, 74 Apoptosis, 338
Amnion, 41 Appendix, 155
Amniotic fluid, 75 Aqueduct, 271
Ampulla, 243 Arachnodactyly, 125
Anal canal, 156 Arch
Anastomosis aortic, 106
post-costal, 219 branchial, 105
post-transverse, 219 hyoid, 105
pre-costal, 217 mandibular, 105
Androgen binding factor, 266 neural, 118
Ancncephaly, 122 pharyngeal, 104, 105
Angioblast, 80 primitive costal, 120
Angioblastic tissue, 200 Area, cardiogenic, 50, 192, 202
Ankyloglossia, 146 Arnold Chiari deformity, 295
Annulus, 10 Arrector pili, 101
Annulus ovalis, 196 Artery
Anodentia, 143 ascending cervical, 219
Anomalies, congenital, 324 axillary, 220
Anonychia, 102 axis, 220
Anophthalmos, 309 brachial, 220
Index
I asked
variety of texts."
Professor Inderbir Singh {MBBS, MS, PhD, FAMS) has a vast teaching experience, spanning over 50 years. He taught anatomy
and embryology at various medical colleges from 1952 to 1989 and retired as Professor of Anatomy, Medical College.
Rohtak. He had been conferred with the title of Professor Emeritus by the M.D. University, Rohtak. Professor Singh has
also published a large number ofresearch papers and books on Gross Anatomy, Histology and Neuroanatomy.
Professor G.P Pal (MBBS. MS, DSc. FASc. FNASc, FAMS) is currently Professor and Head, Department of Anatomy at the
Modern Dental College and Research Centre, Indore. Earlier, he had been Head, Department of Anatomy in various
medical colleges including M.P Shah Medical College, Jamnagar Dr Pal is an eminent teacher and research worker and has
numerous publications to his credit in journals of international repute.
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