Embryo REVIEWnotes

Embryology Dr.
Venkatesh Test 1: Chapters 1-6
Human Embryology – Chapter 1
Embryology: study of the devl’t of an individual before birth
Gonads & Gametes

x Gametes: cells that carry out reproduction
x Fertilization: fusion of male spermatozoon and female ovum = zygote Æ embryo Æ fetus
Chromosomes
x Haploid & Diploid Chromosomes
o Diploid number = 46 chromosomes
o Gametes = haploid = 23 chromosomes
o Zygote = diploid (23 from each parent)
x Autosomes & Sex Chromosomes
o 44 autosomes, 2 sex chromos (X or Y)
o Male = XY, female = XX
o Homologous chromosomes: pair of 2 chromos that are exactly alike
One chromo of each pair from mother and father
o Chromosome Structure
2 chromatids, 1 centromere (kinetochore)
Karyotyping: classification of chromos based on characteristics (ie: length)
o Significance of Chromosomes
Cells get directions from fertilized ovum to carry on all its func’ns throughout life
Genes made of DNA store all information; involved in protein synth
Proteins = enzymes, hormones, antibodies; main constituents of body
x Func’ns of cell depend on the proteins it synthesizes
x Mitosis
o Prophase
Chromatin condenses Æ Chromos are now seen distinctly; centrioles move apart
Nuclear mbrn disappears, spindle forms
o Metaphase
Chromos arranged at equator and att to spindle
o Anaphase
Centromeres split so that ea chromatid becomes an independent chromo
One chromo of each pair moves to either
o Telophase
Nuclear membranes form
Centrioles divide
Chromosomes gradually lengthen and become indistinct
o Interphase (in between cell divisions)
Chromos are in the form of extended threads
DNA of each chromo has undergone duplication
x Meiosis I
o Prophase I: 4 Phases
Leptotene: chromos visible; each has 2 chromatids – can’t distinguish
Zygotene: 2 chromos of each pair lie parallel to eo Æ “bivalent” (synapsis)
Pachytene: 2 chromatids of ea chromo become distinct
x Bivalent has 4 chromatids = “tetrad”; 2 central & 2 peripheral
x Crossing Over bt 2 central chromatids of each chromo
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Embryology Dr. Venkatesh Test 1: Chapters 1-6
x Chiasmata: point of adherence of crossing over

Diplotene: 2 chromos of bivalent try to move apart
x Chromatids involved in crossing over break at points of crossing and loose
pcs attached to other chromatid = genetic exchange
o Metaphase I
nuclear mbrn disappears
spindle forms and chromos are att to it by centromeres
o Anaphase I
One entire chromosome of the pair moves to either pole
Centromeres do not divide
o Telophase I
2 haploid daughter cells formed
x Interphase bt Meiosis I and II has NO DNA DUPLICATION
x Meiosis II
o Similar to mitosis but all 4 daughter cells are genetically different due to crossing over

Spermatogenesis and Oogenesis
Structure of a Mature Spermatozoon

x $SSUR[ȝPORQJ
x Head
o 3LULIRUPVKDSHȝPORQJ
o Derived from nucleus (23 highly condensed chomos)
Chromos extremely condensed Æ head highly resistant to physical stresses
Chem. Basis for condensation is replacement of histones by protamines
o Acrosome: cap-like structure Æ has enzymes that help penetration of spermatozoon into
ovum during fertilization
x Neck
o Basal body: helps est intimate connection bt head & remainder of spermatozoon
Made of 9 segmented rod-like structures
Articular surface on proximal side (towards head) which fits into a depression
(implantation fossa) in head
o Centriole
x Axial Filament
o Begins just behind centrioel; passes thru middle pc and most of tail
o Annulus: ring-link structure through which axial filament passes through
o Spiral sheath: made up of mitochondria, surrounds the part of axial filament in mid pc
o Composed of many fibrils, arranged in a circle
Pair of central fibrils surrounded by 9 doublets
Petal-shaped fibrils – 1 outside each doublet
Fibrous sheath outside fibrils (surround by spirally arranged mito in middle pc)
x Entire spermatozoon enclosed in plasma mbrn
Spermatogenesis
x Formation of spermatozoa during reprod period in males (from 12-16 thru old age)
x Formed in walls of seminiferous tubules of testes
x Spermatogonia (type A) or germ cells - DIPLOID
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o Divide mitotically = Type A & Type B spermatogonia

x Spermatogonia (type B) – DIPLOID
o Enlarge or undergo mitosis to form primary spermatocytes
x Primary spermatocytes – DIPLOID
o Divide so that each forms 2 secondary spermatocytes (haploid)
o First meiotic division
x Secondary spermatocyte – HAPLOID
o Divides to form 2 spermatids
o 2nd meiotic division – NO REDUCTION IN CHROMO #
x Spermatid – HAPLOID
o Transformation Æ Each gradually changes its shape to become a spermatozoon
o Spermatid = circular cell containing a nucleus, Golgi apparatus, centriole & mitochondria
x SPERMIOGENESIS
o Process of transforming spermatid Æ spermatozoon
o Nucleus Æ head
o Golgi Apparatus Æ acrosomic cap
o Centriole Æ divides into 2 Æ one becomes spherical on neck other basal body or annulus
Axial filament grows out of them
o Part of axial filament bt neck & annulus becomes surrounded by mito Æ middle piece
o Remainder of axial fil. Extends to form tail
o Most of the cytoplasm is shed, but cell mbrn still covers spermatozoon
x Spermatogenesis + Spermiogenesis = 2 months
x Maturation & Completion of Spermatozoa
o Current of fluid in seminiferous tubules carries spermatozoa from testis Æ epididymus
o Stored and undergo maturation in epididymus
o Changes take place in glycoproteins of PM covering sperm head
o Become fully motile after ejaculation when mixed with prostate & seminal vesicle secr’n
o Capacitation: Acquire ability to fertilize ovum after they have been in female genital
tract for some time – final step of maturation
Glycoprotein coat and seminal proteins lying over surface of sperm altered
Usually undergo capacitation in uterus or uterine tube
When comes in contact with zona pellucida, changes take place in mbrns over
acrosome and enable the release of lysosomal enzymes – acrosome reaction
Some enzymes help in digesting the z.p and in penetration of sperm thru it
Zona reaction: changes in properties of zona pellucida
x Spermatogenesis vs. Spermiogenesis
o Spermatogenesis: complete process of formation of a sperm from spermatogonium
1st & 2nd meiotic division AND spermiogenesis
o Spermiogenesis: process of transformation of a rounded spermatid to a spermatozoon
Oogenesis
x Cortex of ovary: mainly large round cells Æ oogonia – all to be used in female life is produced
before birth and do not multiply thereafter
x Spermatogenesis vs. Oogenesis
o One primary oocyte only forms ONE OVUM
o When spermatocyte divides, its cytoplasm is equally distributed bt the 2 secondary ones
o When oocyte divides Æ almost ALL cytoplasm goes to daughter cell = 2ndary oocyte
Other daughter (1st polar body) gets ½ chromos but barely any cytoplasm
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st
1 polar body formed just to get rid of unwanted chromos
x Further Details
o Late fetal period – primary oogonia enlarge Æ primary oocytes
o At birth – all primary oocytes (~40,000) in prophase of 1st meiotic; remain in Prophase I
until they begin to mature and are ready to ovulate
o Female reproductive period bt 12 – 50 yrs
o With each menstrual cycle, few primary oocytes (~5-30) begin to mature and complete
first meiotic division shortly before ovulation
o 1st meiotic division = secondary oocyte + 1st polar body
o Secondary oocyte Æ Meiosis II
Ovulation while oocyte in metaphase; remains in meta until fertilization
Meiosis II completed only if fertilization occurs
If no fertilization degenerates about 24 hrs after ovulation
o Only 1 oocyte reaches maturity and is ovulated per cycle
o Dur entire reproductive life of female, only 400 ova discharged
x Formation of Ovarian Follicles
o Stromal cells Æ ovarian or Graafian follicles – surround ova and protect them
o Some cells of stroma become flattened and surround an oocyte Æ follicular cells
o Flattened follicular cells become columnar Æ primordial follicles
o Zona pellucida: homogeneous mbrn appears bt follicular cells & oocyte
o Follicular cells prolif to form several layers = membrana granulosa Æ granulosa cells
o A cavity (antrum) appears within the membrane Æ follicle formed
o Cavity rapidly increases in size = wall of granulosa cells becomes thin; oocyte lies
eccentrically in follicle surr by cumulus oophoricus
o Discus proligerus: cells that attach oocyte to wall of follicle
o as follicle expands, stromal cells surrounding membrane granulosa become condensed to
form theca interna – secrete oestrogen Æ “cells of thecal gland”
o outside theca interna some fibrous tissue becomes condensed to form another covering
for follicle – theca externa Æ ovarian follicle fully formed
x Interdependence of Oocyte & Follicular Cells
o Both oocyte and surr follicular cell dependent on eo for further devl’t
o Follicular cells secrete meiotic inhibitory factors, which prevent primary oocytes from
maturing beyond prophase of first meiotic division Æ effect can last many years
o Inhibitory factors transmitted to oocyte via gap junctions present bt microvilli of oocytes
and of follicular cells (zona pellucida)
o Follicular cells also rsp for growth, metabo, maturation of oocytes
o Oocytes resp for proliferation & diff of follicular cells
o Factors produced in oocyte help formation & aturation of Graafian follicles
x Ovulation
o Ovum enlarges and follicle ruptures then shed from ovary
o Just before, follicle diam = 15mm, stroma & theca on this side of follicle very thin
o Stigma: avascular area appears over most convex point of follicle
o Cells in cumulus oophoricus become loosened by accum of ICF bt them
o Factors leading to ovulation:
Ĺ/+FRQF = Ĺ activity of collagenase – digests collagen fibers around follicle
Ĺ prostaglandins = contraction of smooth muscle in ovary wall
Ĺ pressure of fluid in follicular cavity
Enzymatic digestion of follicular wall is main factor responsible
x Structure of Ovum
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o Ovum shed from ovary is not fully mature

o Ovum surr by zona pellucida. Some cells of corona radiate seen sticking outside of zona
pellucida
No nucleus seen since nuc mbrn dissolved from Meiosis II
Perivitelline space bt z.p & vitelline mbrn (cell mbrn); contains 1st polar body
o Ovum very large at time of ovulation
x Fate of the Ovum
o Ovum easily carried into FT by follicular fluid and ciliated cells lining tube
o Slowly travels thru FT Æ uterus (3-4 days), if have sex, sperm Æ tube = fertilization
If fertilized Æ embryo Æ implanted in uterine wall
No fertilization Æ ovum dies in 12-24 hrs passes thru uterus into vagina
x Corpus Luteum
o Main Function: secrete progesterone & some estrogen
o From ruptured follicle, ruptures as follows:
Wall collapses & becomes folded
Follicular cells are small & rounded then rapidly enlarge Æ cells squish together
= polyhedral shape Æ cyto filled with lutein (yellow pigment) Æ luteal cells;
some cells of theca interna also enlarge & contribute to corpus luteum
Prog secr’ns has to be poured into blood like secr’ns of endocrine glands (ovarian
follicle AVASCULAR, but surr theca interna is full of blood vessels)
Blood supplied by theca interna when corpus luteum forms
o Not fertilized Æ corpus luteum persists for 14 days, secretes progesterone; at end of its
func’l life, degenerates and forms mass of fibrous tissue Æ corpus albicans
o If fertilized Æ pregnancy; persists for 3-4 mths; corpus luteum of pregnancy
may occupy 1/3 – ½ total volume of ovary
Progesterone secreted is essential for maint of pregnancy in first few mths
After 4th month, corpus luteum not needed bc placenta begins to secrete prog
hCG prevents c.l frm degenerating in early; sec by trophoblast cells of embryo
o Ovarian Cycle: series of changes that begin with formation of ovarian follicle and end
with degen of c.l; ~28 days, ovulation on 14th
x Fate of Ovarian Follicles
o Follicles that don’t reach maturity undergo degeneration – ovum & gran cells disappear
o Interstitial glands (corpora atretica): formed by prolif of theca interna Æ sec estrogen
x Ovarian Cycle and Hormones
o Influenced by hormones produced by hypophysis cerebri
o Hormones of theca interna and corpus lutetium influence other parts of reprod sys
x Reproductive Period
o Viability of Gametes
Ovum usually degens 24hrs after ovulation, sperm usually 48 hrs after ejacul’n
Abnormalities in Formation of Gametes

x Abnormalities of Form
o Sperm: may be too large or too small, head body or tail duplicated
o Ovum: may have too lg nucleus or 2 nuclei, 2 oocytes may be seen in one follicle
x Chromosomal Abnormalities
o Non-disjunction: During Meiosis I, chromos don’t separate in anaphase; chromo has 24
Trisomy: zygote has 47 chromos (3 identical chromos instead of 1 normal pair)
x Chromo 21 Æ Down’s Syndrome
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o broad face, obliquely placed palpebral fissures, epicanthus,

furrowed lower lip, broad hands, single transverse crease, MR &
heart problems
x extra X or Y chromo can give rise to various syndromes assoc with
abnormal genital devl’t, MR and abnormal growth
o XXY: abnormal female
o XXY: klinefelter’s syndrome – abnormal male
Male but testes poorly devl’pd = sterility, gynecomastia
o XYY: abnormal male
o XXX: 2 masses of sex chromatin – ‘super females’, but poor devl’t
o Monosomy: both chromos of pair go to 1 gamete (22 chromos instead of 23)
Zygote Æ45 chromos
x Turner’s Syndrome: only one X chromo
o Agenesis of ovaries
o MR, skeletal abnormalities, folds of skin on neck (webbed neck)
o One pair may be rep’d by more than 3 chromos
XXXY, XXXXY, XXYY, XXXX
o Triploidy: gamete may be diploid zygote will have 46+23 = 69 chromos
o Abnormalities in crossing over
Translocation: part of chromo att to chromo of different pair
Deletion: part of chromo may be lost
Duplication: 2 chromos of pair break at unequal distances then joins opposite
chromosome; one chromo longer than normal – some genes duplicated, some
genes missing
Inversion: pc separating from chromo may get inverted before joining opp
chromo, same genes present but sequences disturbed
o Isochromosomes: formed when centromere splites transversely = 2 dissimilar chromos
MosaicismMay also occur during segmentation of ovum = fetus with normal &
abnormal chromos
x Gene Abnormalities (Gene Mutations)
o Change in structure of gene may occur at time of gametogenesis = birth defects
o Gene Mutation: change in structure & function of gene

The Menstrual Cycle
Structure of the Uterus

x Perimetrium: outermost layer, made of peritoneum
x Myometrium: makes up main thickness of the wall, made up of smooth muscle
x Endometrium: innermost, undergoes changes during menstrual cycle
o Surface covered by lining epith
o Stroma contains uterine glands fills space bt epith & myometrium
o Arteries run vertically towards surface; some spirally and supply whole thickness of
endomet, others straight and confined to basal part
Phases of the Mestrual Cycle

x Follicular Phase
o Postmenstrual (Days 5-8)
o Proliferative (Days 9-18)
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o Oestrogens produced by developing follicles = changes

o 1st half of menstrual cycle
o Ovulation occurs on Day 14
x Luteal Phase
o Secretory/Premenstrual (Days 19-28)
o After ovulation, corpus luteum formed & starts secreted Progesterone
o Progesterone + oestrogen = changes in endometrium
o Endomet thick, soft, richly supplied with blood, nutrition provided by u glands
o Before next bleeding = ĻSURJ RHVWURJHQVÆ withdrawal of hormones = bleeding
x Menstrual (Days 1-4)
o Few hours before, spiral arteries get constricted so blood supply is cut off = ischemia
o Degeneration of endometrium & damage to wall of blood vessels
o When arteries relax & blood flows again, leaks out into endomet thru damaged BVs
x Sequence of Events
1. Endometrium gradually thickens from 0.5 mm Æ 7 mm
2. Uterine glands lengthen and become convoluted (basal parts stay tubular)
3. During postmenstrual phase, lining cuboidal, during proliferative, columnar. Glycogen
accumulates in basal portion = nucleus pushed towards lumen; apical part of cell shed
during secretory phase Æ cell becomes cuboidal again with luminar edge irregular
4. as endometrium thickens, stroma can be divided into 3 layers:
a. Stratum compactum Æ superficial part of stroma
b. Stratum spongiosum Æ stroma surrounding uterine glands
c. Stratum basal Æ deepest part of stroma
5. arteries of endomet grow dur prolif phase; dur secretory phase, arteries supplying
superficial 2/3 called spiral arteries. Basal 1/3 doesn’t change in cycle – remains straight
& short.
x If no pregnancy: stratum compactum & spongiosum shed off = bleeding
x Cervical mucosa is not affected
x Time of Ovulation in Relation to Menstruation
o Occurs on Day 14 – middle of cycle
o Body temp low during menstruation, subsequently rises
o Sudden fall in temperature followed by a rise = OVULATION
Clinical Correlation
x Importance of determining the Time of Ovulation and ‘Safe Period’
o Where pregnancy is not desired
x After ovulation, ovum can be fertilized within 2 days
x Sperm die within 4 days after entering vagina
x Fertilization only occurs if have sex bt 4 days before & 2 days after ovulation
o Where pregnancy is desired
x Knowledge important in cases of sterility; couple can be advised when to try
x Correlation bt Ovarian & Uterine Cycles
o Both are 28 days long
o Uterine cycle dependent on ovarian cycle
o Uterine endomet shows cyclic changes – dependent on hormones secreted by developing
ovarian follicles & corpus luteum of ovary
Hormonal Control of Ovarian & Uterine Cycles
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x Hypothalamus = major control center of reproduction

o GnRH controls secretion of gonadotrophic hormones by anterior pituitary
FSH Æ stimulates formation & maturation of ovarian follicles
x Maturing follicles secrete oestrogens = repair & prolif of endomet
x Oestrogens peak 2 days before ovulation = LH surge 24-36 hrs b4 ovul’n
LH Æ ovulation & Graafian follicle transformed into corpus luteum
x Stimulates secr’n of progesterone from corpus luteum
x Combined action of oestrogen & progesterone stimulates endometrial
glands to secrete glycogen rich mucoid material
x No fertilization Æ granulosa cells produce inhibin Æ ant pit Æ inhibits secretion of GnH =
regression of corpus luteum
o Fall in blood level of estrogen & progesterone
o Endometrum regresses Æ menstruation
x Fertilization Æ no regression; progesterone & oestrogen cont to be secreted
Clinical Correlation
x Use of Hormones for Contraception
o Progestins: synthetic; better results when small amount of oestrogen given
o Norethisterone acetate (1 mg) + oestradiol (50 ȝJ
Pack of 28 Æ 21 = hormonal, 7 = nothing
Start 5 days after onset of menstruation
o Progesterone inhibits FSH & LH secretion Æ interferes with maturation of follicles &
ovulation
o Stopping use = withdrawal of hormones Æ menstruation

Formation of Germ Layers
x Morula: 16 cells
x Trophoblast: outer layer of cells covering inner cell mass of morula
x Blastocyst: fluid partially separates inner cell mass from trophoblast
x Embryonic disc: formed by rearrangement & multiplication of cells of inner mass
o 2 germ layers Æ ectoderm & endoderm
o Mesoderm forms later between endo & ecto
x Amniotic cavity: formed on ectodermal & endodermal sides = yolk sac
x Extra-embryonic mesoderm: separates walls of cavity from trophoblast
x Extra-embryonic coelom: splits e-e meso into 2 layers:
o Somatopleuric Æ in contact with trophoblast
o Splanchnopleuric Æ in contact with yolk sac
x Chorion: trophoblast + somatopleuric
x Amnion: cells forming wall of amniotic cavity
x Connecting Stalk: attaches amniotic cavity to trophoblast
x Prochordal Plate: ectoderm & endoderm not separated
x Primitive Streak: embryonic disc divided into right & left
x Mesoderm: formed by cells multiplying in primitive streak Æ bt endo & ecto
x Cloacal Membrane: caudal to primitive disc Æ only endo & ecto
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Fertilization
x Occurs at the ampulla of uterine tube; only 1 sperm penetrates zona pellucida
x As soon as sperm enters ovum, meiosis II is complete
x Female pronucleus: nucleus of ovum after fertilization
x Male pronucleus: transformation of head of sperm after separates from middle piece and tail
x Pronuclei lose their nuclear membranes and chromos from each get mixed together
x Mitosis = 2-celled embryo
x Biochemical Changes Occuring during Fertilization
o Glycoprotein of zona pellucida = induction of acrosomal reaction Æ penetrate thru z.p
o Plasma mbrns of sperm & oocyte fuse at receptor sites; head & tail enter cyto of ovum
o Changes in PM of oocyte & z.p ensure that no other sperm can enter oocyte
o Zona reaction: z.p altered due to release of lysosomal enzy by PM of oocyte
o As soon as sperm enters ovum – Meiosis II complete & 2nd polar body formed
o Entry of sperm = metabolic changes within ovum Æ devlp into embryo
o Before mitosis, each pronuclei undergoes DNA replication to form 2nd chromatid
o Mitosis = 2 cells with 46 chromos (from sperm AND ovum)
o As a result of fertilization
Diploid number restored
Determination of sex
Fertilized ovum undergoes cleavage (divides into many cells)
o 2 daughter cells are still surrounded by zona pellucida
o Each daughter cell is much smaller than ovum
o As embryo divides more and more, cells become smaller and smaller
x Test Tube Babies
o In vitro fertilization
o Gonadotroins admin’d to woman to stimulate growth of follicles in ovary
o Ovum removed by an aspirator just before ovulation then added with sperm in a medium
o Fertilization and early devl’t of embryo take place in medium
o Embryo moved to uterus when reaches 8-cell stage
Sex Determination
x Girl Æ sperm is X-bearing, zygote = 44 + X + X
x Boy Æ sperm is Y-bearing, zygote = 44 + X + Y
x Determined at fertilization
Cleavage
x One cell divides at a time
x Morula: 16-cell stage, still surrounded by z.p
o Inner cell mass Æ “embryoblast”
o Outer layer Æ trophoblast – help provide nutrition to embryo
x Fluid from uterine cavity separates layers of morula; as fluid increases Æ cyst
x Blastocyst: cells of trophoblast flattened & inner mass att on one side of trophoblast
o Blastocoele: cavity of blastocyst
o Embryonic/animal pole: side that is att to inner cell mass
o Abembryonic pole: opposite side
x Function of Zona Pellucida
o Trophoblast can stick to epithelium and its cells can ‘eat up’ other cells
Can invade and burrow into tissues which it contacts
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Z.p prevents it from sticking as it moves down tube; receives substances stored
within ovum (yolk) & by diffusions from uterine secretions
blastocyst needs additional sources of nutrition Æ sticks to uterine endometrium
o z.p disappears after morula reaches uterine lumen
o z.p prevents implantation of blastocyst at an abnormal site
o z.p acts as barrier that separates embryonic & maternal tissues to prevent
immunological reactions
when z.p disappears, various immunosuppressive cytokinase and proteins are
produced by implanting embryo – blocks mother from thinking its foreign
Formation of Germ Layers

x embryonic disc: 3-layered Æ endoderm, ectoderm, mesoderm
1. Formation of endoderm Æ some cells of inner cell mass flattened

2. Formation of ectoderm Æ remaining cells of inner cell mass columnar
3. Amniotic cavity: space between ectoderm (below) & trophoblast (above)
a. Amniotic fluid fills cavity
b. Amniogenic cells derived from trophoblast, line roof of cavity
c. Floor formed by ectoderm
4. Heuser’s membrane: lining of flattened cells from endoderm inside blastocystic cavity
a. primary yolk sac Æ cavity lined on all sides by cells originated from endoderm
5. Extra-embryonic mesoderm: originate from cells of tropho; lies bt tropho and flattened endo
cells around yolk sac and also separates wall of amniotic cavity from trophoblast
a. Lies outside embryonic disc, doesn’t give rise to any tissues of embryo
6. Extra-embryonic coelom: splits e-e meso into 2 layers
a. Parietal/somatopleuric extra-embryonic mesoderm: lines inside tropho & outside
amniotic cavity
b. Visceral/splanchnopleuric extra-embryonic mesoderm: lines outside yolk sac
c. Connecting stalk: unsplit part of meso, keeps devlp’g embryo attached to blastocyst wall
7. Formation of Chorion & Amnion
a. Chorion: mbrn formed by parietal e-e meso & trophoblast
b. Amnion: mbrn constituted by amniogenic cells = wall of amniotic cavity
c. Important role in child birth
8. Secondary Yolk Sac: e-e meso & e-e coelom Æ sac becomes much smaller; cuboidal cells
9. embryo = circular, 2 layers (endo twrds yolk sac = cuboidal & ecto near amniotic cav, columnar
10. prochordal plate: area of endoderm where cells become columnar = central axis of embryo;
divided into right & left and can distinguish future sites of head & tail
11. primitive streak: bulge formed when ectodermal near central axis near tail-end begin to
proliferate; from rounded or oval swelling, becomes linear structure in central axis of disc
12. cells proliferating near prim streak push themselves bt endo & ecto Æ intra-embryonic meso
13. meso extends cranial to prochordal plate – becomes cont’s across midline; forms most of tissues
of body; no meso in prochordal plate – region very thin Æ bucco-pharyngeal mbrn
14. disc and primitive streak gradually elongate
15. as embryonic disc enlarges – connecting stalk becomes smaller & confined to tail end of disc
16. cloacal membrane Æ mesoderm from primitive streak passes thru into connecting stalk
Alternative View of Formation of Germ Layers

x ectoderm (columnar) Æ epiblast
x endoderm (cuboidal) Æ hypoblast
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x some cells of epi- migrate to primitive streak Æ mesoderm

x other cells push hypoblast aside = endoderm and those that remain = ectoderm
x all 3 germ layers derived from epiblast
x prochardal plate and neural crest also form some intra-embryonic mesoderm
Use of Stem Cells in Treatment of Diseases

x embryonic stem cells: cells of inner cell mass, differentiate into 3 layers Æ all tissues & organs
x can be grown in culture Æ various adult cells
x when introduced in tissues of living person, local enviro helps cells diff into surr cell types
x Used to treat many diseases:
o Parkinson’s
o Alzheimer
o Diabetes
o Myocardial infarction
o Blood diseases
o Severe burns
o Osteoporosis
o Spinal cord injury…
x Immune rejection is possible Æ under study “therapeutic stem cell cloning”
x Adult stem cells can be taken from bone marrow, brain, skeletal muscle Æ difficult in culture
Timetable of Events
x Pre-organogenesis period: devl’t from fertilization Æ formation of bilaminar disc (14 days)
o Teratogens introduced dur this period = death
x Gastrulation: primitive streak, intra-embryonic meso (begins in 3rd week)
x Embryonic period: from 3rd week; teratogens introduced here Æ congenital anomalies
Age (days) Developmental Events

2 Embryo at 2-cell stage
3 Morula formed
4 Blastocyst formed
8 Bilaminar disc formed
14 Prochordal plate & primitive streak seen
16 Intra-embryonic mesoderm is formed/disk is now 3-layered.

Further Development of Embryonic Disc
x Primitive knot: enlargement of cranial end of primitive streak

x Notochordal process: cells of primitive knot multiply & pass cranially = rod-like structure that
reaching up to prochrodal plate
x Notochord: formed when prochordal plate converted back into rod-like structure
x Nucleus pulposus: remnants of notochord; found in each intervertebral disc
x Neural plate: wide strip of ectoderm overlying notochord that becomes thickened, brain & spinal
cord develop from here
x Intra-embryonic mesoderm = 3 subdivisions
o Paraxial mesoderm: next to middle line; segmentation Æ somites
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o Lateral plate mesoderm

Intra-embryonic coelom: cavity that splits meso into somatopleuric (contact with
ectoderm) & splanchnopleuric layers (contact with endoderm)
x Later forms pericardial, pleural & peritoneal cavities
o Intermediate mesoderm: strip of mesoderm bt lateral plate & paraxial mesoderm
x Head & tail folds & lateral folds of embryonic disc Æ foregut, midgut, hindgut
x Buccopharyngeal membrane: prochordal plate that closes cranial end of gut
x Cloacal membrane: closes gut caudally
x Umbilical cord: develops from connecting stalk; covered by amnion
o R & L umbilical arteries, L umbilical vein, remnants of vitello-intestinal duct & yolk sac
o Ground substance made of Wharton’s jelly from mesoderm
x Allantoic diverticulum: from yolk sac b4 form’n of gut; after tail fold Æ diverticulum of hindgut
x Pericardial cavity: from intra-embryonic coelom that lies cranially to prochordal plate;
developing heart is ventral
o After head fold, pericardial cavity lies ventral to foregut & developing heart is dorsal to
pericardial cavity
x Septum transversarum: made of intra-emb meso that lies cranial to pericardial cavity; after head
fold, caudal to pericardium & heart; liver & diaphragm devl’p in relation to septum transversum
Formation of the Notochord

x Notochord: midline sstructure, develops in region lying bt cranial end of primitive streak 7
caudal end of prochordal plate; several stages of development:
o Cranial end of primitive streak becomes thickened Æ primitive knot
o Blastopore: depression that appears in center of primitive knot
o cells in primitive knot multiply and pass cranially in middle line between ectoderm &
endoderm Æ caudal margin of prochordal plate Æ notochordal process
o cells of notochordal process undergo several stages of rearrangement Æ notochord
x elongates as embryo grows; lies in area where spine will go, BUT notochord does NOT give
rise to vertebral column; most of it disappears, but parts persist in region of each intervertebral
disc Æ nucleus pulposus
x More Details…
o After blastopore is formed, cavity extends into notochordal process Æ notochordal canal
o Cells forming floor of canal become intercalated with endo cells Æ separate canal from
cavity of yolk sac
o Floor of canal begins to break down to comm. w/ yolk sac, and amniotic cavity (through
blastopore) Æ amniotic cavity and yolk sac are now in communication with e.o
o Walls of canal gradually flatten Æ notochordal plate
o Flattening process reversed and plate becomes curved again = shape of tube; prolif of
cells of tube Æ solid rod of cells Æ notochord; complete separated from endoderm
Formation of the Neural Tube - Neurulation

x Neural tube gives rise to the brain & spinal cord
x From ectoderm overlying notochord & extends from prochordal plate Æ primitive knot
x Divides into:
o Cranial enlarged part that forms brain
o Caudal tubular part that forms spinal cord
x Developing brain forms large conspicuous mass on dorsal aspect
12
Subdivision of Intra-Embryonic Mesoderm

x Separates ectoderm and endoderm except in:
o Prochordal plate
o Cloacal membrane
o In midline caudal to prochordal plate (place for notochord)
x Mesoderm meets cranially to prochordal plate at midline, continuous with e-e meso, divides into:
o Paraxial mesoderm: on either side of notochord, becomes thick
Becomes segmented into cubical masses Æ somitomeres Æ somites
First somites seen on either side of midline behind prochordal plate
More somites formed caudally on either side of developing neural tube
o Lateral plate mesoderm: more laterally, forms thinner layer
o Intermediate mesoderm: between paraxial & lateral
Formation of the Intra-Embryonic Coelom

x Intra-embryonic coelom: cavities that appear in lateral plate meso come together
x 2 haves joined together crania to prochordal plate
x Comm. with extra-embryonic coelom Æ lat. Plate meso slpits:
o Somatopleuric/parietal: i-e mes that is in contact with ectoderm
o Splanchnopleuric/visceral: i-e embryonic meso that is in contact with endoderm
o Septum transversum: 2 divisions continuous cranial to cardiogenic area bc i-e coelom
hasn’t extended into it
x i-e coelom Æ pericardial, pleural & peritoneal cavities
o pericardium: formed from part of i-e coelom in midline, cranial to prochordal plate
o cardiogenic area: cranial to cardiogenic area
Yolk Sac and Folding of Embryo

x primary yolk sac Æ bounded above by cubical endoderm of embryonic disc and flattened cells
of blastocystic cavity everywhere else
x secondary yolk sac Æ smaller with formation of e-e meso and e-e coelom
x progressive increase in size of embryonic disc
x head & tail of disc remain close together = ĹOHQJWKRIGLVFÆ bulge upwards into amniotic cavity
x disc grows bigger Æ folded on itself at head & tail Æ head & tail folds
x folds = enclose parts of yolk sac w/in embryo Æ primitive gut – tube formed by endoderm
x only midgut communicates with yolk sac; foregut (cranial) & hindgut (caudal) don’t comm.
x comm. to yolk sac becomes narrower and narrower Æ definitive yolk sac
x vitello-intestinal duct Æ narrow channel that connects def yolk sac to gut; eventually disappears
x lateral folds Æ encloses embryo all the way around by ectoderm
x umbilical opening: except in the region where intestinal duct passes
x as embryonic disc folds on itself, gets bigger Æ surrounds embryo on all sides; embryo floats in
amniotic fluid in cavity
Connecting Stalk
x embryo & amniotic cavity & yolk sac remain in tact to trophoblast by e-e meso Æ conn. Stalk
x only connecting link bt embryo and placenta
x as embryo grows, area of attachment of stalk becomes smaller; only seen at caudal end
o att moves with tail end to ventral aspect of embryo & attached in area of umb opening
x blood vessels in embryo comm. with BVs in placenta thru connecting stalk
o first there are 2 arteries, 2 veins; later right vein disappears
13
o amnion has circular att to margins of umbilical opening Æ wide tube for:
Vitello-intestinal duct & remnants of yolk sac
E-e meso of stalk; converted into Wharton’s jelly – protects BV in umbilical cord
BVs from embryo Æ placenta
Small part of extra-embryonic coelom
x Umbilical cord: progressively lengthens so embryo can move w/in amniotic cavity
o at birth: umbilical cord ~0.5 m long, ~2cm diam
o umbilical cord that is too short or too long = problems during delivery
Allantoic Diverticulum
x arises from yolk sac before tail fold; caudal end of embryonic disc
x after tail fold, part of diverticulum absorbed into hindgut into connecting stalk
x leads to devl’t of urinary bladder
Effect of Head & Tail Folds on Positions of Other Structures

x before formation of head & tail folds, structures at midline from cranial Æ caudal:
o septum transversarum
o developing pericardial cavity and heart
o prochordal plate
o neural plate
o primitive streak
o cloacal membrane
x after head fold, pericardial cavity comes to ventral side of embryo Æ heart in roof of cavity;
pericardium grows and forms bulging on ventral side of embryo
x septum transversarum caudal to heart; later Æ diaphragm & liver devl’p in relation to septum
x prochordal plate Æ buccopharyngeal (oral) closes foregut; when breaks down, comm. w/ ext
x most cranial structure becomes enlarged cranial part of neural tube Æ brain
o 2 big bulgings on ventral aspect of embryo:
Cranial: developing brain
Slightly below: pericardium
Stomatodaeum: depression bt brain & heart; floor = buccopharyngeal mbrn
x Primitive streak now inconspicuous twrds tail end of embryo, gradually disappears
o Distal end of hindgut closed by cloacal mbrn (first caudally, then faces ventrally)
Additional Points
x In later life, remnants of primitive streak Æ tumors that have tissues from all 3 germ layers;
mostly seen in sacral region – sacrococcygeal tumors
x Formation of neural tube induced by notochord
x Somitomeres are not confined to region of somits; in head, somitomeres Æ mesenchyme
x Wharton’s jelly rich in proteoglycans
Timetable of Events in this Chapter

Primitive streak appears
15
Definitive yolk sac formed
Notochordal process appears
17
Heart tube is seen in cardiogenic area
14
Allantoic diverticulum is seen

Intra-embryonic mesoderm is being formed
19
Connecting stalk can be distinguished
Neural groove is seen
21
Head fold begins to fold
23 Closure of neural tube is seen

The Placenta
x Implantation: developing embryo gets attached to endometrium

x Interstitial implantation: embryo is buried into the wall of the endometrium
x Decidua: refers to endometrium after implantation
x Placenta: formed from embryonic structures & decidua Æ transport nutrients & oxy to fetus;
removal of waste products also occurs through placenta
o Chorionic villi: surr by maternal blood, fetal blood circulates thru capillaries in villi
o Placental membrane: separates maternal & fetal blood
o Chorion: fetal tissue that contributes to formation of placenta; trophoblast on e-e meso
x Trophoblast proliferates into 2 layers:
o Cytotrophoblast - cellular
o Syncytiotrophoblast – cytoplasm with nuclei, but no cell boundaries
x Primary villi: central core cytotrophoblast covered by syncytiotrophoblast
x Secondary villi: 3 layers, e-e meso Æ cytotrophoblast Æ syncytiotrophoblast
x Tertiary villi: blood capillaries in e-e mesoderm
x Maternal blood flows through intervillus space; as placenta enlarges, septa grow & divide
placenta into lobes; fully formed placenta = 6” diameter & 500g wt
x Placenta praevia: when placenta attaches lower in body of uterus (vs. upper) Æ problems
x Amniotic cavity Æ as grows bigger, e-e coelom goes away & amnion & chorion fuse; as
enlarges further, uterine cavity obliterated & amnion & chorion (membranes) bulge into cervix
x Extra-embryonic coelom
x Uterine cavity
Implantation Æ 6th day of fertilization

x Zygote is already at morula stage by the time it reaches the uterus
x z.p prevents the zygote from sticking to the wall of the tube
x when z.p disappears, the trophoblastic cells allow the zygote to attach itself on the uterine wall
x interstitial implantation: trophoblast of blastocyst embeds itself deeper and deeper into endomet
x proteolytic enzymes are produced by trophoblast to aid in implantation
x trophoblastic cells that are over the inner cell mass, penetrate the epith of endometrium
x mutual interaction bt trophoblastic cells & endometrium mediated by receptors present on uterine
epith & secretion of L-selectin, & integrins by trophoblast cells
Decidua
x when morula reaches uterus, endometrium in secretory phase, these features stay once
implantation occurs to support zygote
x decidual reaction: stromal cells enlarge, become vacuolated to store glycogen & lipids
x decidua basalis: aka decidual plate; portion of decidua where placenta will form
o contains large decidual cells that store lipids & glycogen Æ nutrition to embryo
15
o firmly united to chorion

x decidua capsularis: separates embryo from uterine lumen
x decidua parietalis: lines rest of uterine cavity
x upon delivery, decidua shed off with placenta and membranes
Formation of Chorionic Villi

x surrounded by maternal blood
x capillaries inside villi circulate fetal blood
x exchanges bt maternal & fetal circulations take place thru tissues in walls of villi
x projections of trophoblast and extra-embryonic meso; grow into surrounding decidua
x villi that go into decidua capsularis degen & this part of chorion smooth Æ chrion laevae
x villi that grow into basalis form disc-shaped mass Æ chorion frondosum Æ placenta
x Primary Villi: central core of cytotropho surr by syncytiotrophoblast
x Secondary Villi: 3 layers Æ syncytiotrophoblast Æ cytotrophoblast Æ e-e meso
x Tertiary Villi: blood capillaries in mesoderm
x Syncytiotrophoblast grows rapidly and becomes thick; lacunae appear and gradually lie radially
around blastocyst; they are separated by trabeculae (partitions of syncytium)
o Lacunae gradually comm. w/ eo Æ form’n of large lacunar space surrounding trabeculus
x Syncytiotrophoblast grows into endometrium which has eroded so that some of its BVs are open-
up Æ blood fills lacunar space
x Cytotrophoblast cells begin to multiply and grow into each trabeculus Æ central core Æ primary
x E-e meso invades center of each primary villus Æ secondary villi
x Blood vessels formed in meso in core of each villus Æ tertiary
x Fetal blood circulates through villi and maternal blood through intervillous space
x Cytotrophoblastic shell: layer of cells that emerge through syncytium of each villus; spread out
to form layer that completely cuts off syncytium from decidua; these cells rapidly multiply and
placenta grows larger
x Anchoring villi: villi first formed attached to embryonic meso on fetal side and to maternal side
on cytotrophoblastic shell
o Truncus chorii: stem of anchoring villi
o Ramuli chorii: fine branches of truncus; attached to cytotrophoblastic shell
o Free villi branch off into intervillous space – whole space filled with villi = increased
surface area for exchanges bt maternal & fetal circulation
Further Development of Placenta

x Maternal cotyledon: refers to each lobe of placenta, separated by septa; approx 15-20 lobes
x Each lobe has anchoring villi and corresponding branches, Fetal cotyledon (~60-100 in placenta)
x At 9 months, placenta ~6-8” diameter & 500g
x After delivery, shed off with decidua; maternal surface (formed by decidual plate) is rough and
subdivided into cotyledons
x Fetal surface (chorionic plate) lined by amnion; smooth, umbilical cord att to this surface
x Placental Membrane
o Separates maternal from fetal blood; made up of layers of villus wall:
x Endothelium of fetal BVs & its basement mbrn
x Surrounding mesoderm (connective tissue)
x Cytotrophoblast & its BM
16
x Syncytiotrophoblast
o All interchanges of oxygen, nutrition & waste take place here
o Total area ~ 4-14 sq m Æ greater surface area = more effective exchanges
o Efficiency increased in later part of pregnancy when cytotropho layer disappears and CT
thins so that thickness of mbrn goes from 0.025 mm thick Æ 0.002 mm
o Towards end of pregnancy, fibrinoid deposit appears which reduces efficiency
x Functions of Placenta
o Transport of O2, water, electrolytes, carbs, lipids, polypeptides, AAs & vitamins from
maternal Æ fetal blood; full term fetus takes upto 25 mL O2/min
o Excretion of CO2, urea & other waste products from fetus Æ maternal blood
o Maternal Abs (IgG) = immunity against some infections (ie: diphtheria & measles)
o Prevents bacteria and other harmful substances from reaching fetus; but viruses and
bacteria & drugs can pass through Æ congenital malformations
o Maternal hormones don’t reach fetus, but synthesis of progestins & synthetic
oestrogens (ie:: diethylstilbestrol) easily cross placenta and can have adverse effects
on fetus (even carcinoma in later life)
o Keeps blood streams separate Æ prevents antigenic reactions between them
o Synthesizes hormones in syncytiotrophoblast
x Progesterone Æ maint of pregnancy after 4th month (when corpus luteum degens)
x Oestrogens (estriol) Æ maternal blood; promote uterine growth and development
of mammary gland
o Human chorionic gonadotropin (hCG) produced by placenta; similar to LH;
Gonadotropins excreted through maternal urine Æ used to detect pregnancy
o Somatomammotropin (hCS) has an anti-insulin effect on mother = increased plasma
levels of glucose and AAs in maternal circulation; increases availability of these
materials for fetus; enhances glucose utilization by the fetus
o Circulation of Blood through Placenta
x Blood flow thru lacunar spaces in syncytiotropho begins at 9th day
x Blood enters intervillous space through maternal arteries that open into it;
pressure of blood drives it right to the chorionic plate
x Blood in spaces is drained by veins that also open into these spaces
x In fully formed placenta, intervillous spaces contain ~150 mL of blood which can
be replaced in 15-20 seconds (3-4x/min)
Normal Site of Implantation of the Ovum

x Upper uterine segment Æ fundus & greater part of body; enlarges dur pregnancy; placenta here
x Lower uterine segment Æ lower part of body
Abnormal Sites of Implantation of Ovum

x Abnormal Implantation within Uterus
o Placenta praevia: placenta attaches in lower uterine segment
Problems during delivery Æ severe bleeding; various degrees:
First Degree: attaches in lower segment but doesn’t reach the internal os
Second Degree: margin of the placenta reaches the internal os, ut doesn’t cover it
Third Degree: edge of placenta covers the internal os, but when the os dilates
during childbirth, placenta no longer occludes it
Fourth Degree: completely covers internal os & occludes it after dilates
x Implantation outside Uterus
17
o Ectopic Pregnancy: ovum gets implanted anywhere outside uterus

Tubal pregnancy: blastocyst is implanted in uterine tube – doesn’t make it to full
term & may result in rupture of tube Æ leads to abdominal pregnancy
Interstitial tubal implantation: blastocyst implanted in part of uterine tube
passing thru uterine wall
Implantation in the ovary: fertilization and implantation occur while in ovary
x Other Anomalies of Placenta –
o instead of being shaped like a disc, may be:
Bidiscoidal: has 2 discs
Lobed: divided into lobes
Diffuse: chorionic villi persist all around blastocyst – placenta thin and not disc
Placenta succenturiata: small part of placenta separated from rest of it
Fenestrated: hole in disc
Circumvallate: peripheral edge of placenta covered by circular fold of decidua
o Umbilical cord may not be attached to placenta near the center, instead:
Marginal (aka Battledore placenta): cord att to margin of placenta
Furcate: blood vessels divide before reaching placenta
Velamentous insertion: BVs att to amnion & ramify before reaching placenta
Mutual Relationship of Amniotic Cavity, Extra-Embryonic Coelom & Uterine Cavity

x Outer wall of e-e coelom formed by chorion & inner wall by amnion
x As amniotic cavity grows, e-e coelom decreases and eventually disappears when amnion &
chorion fuse Æ amniochorionic membrane
x As amniotic cavity expands further, uterine cavity gradually disappears as Decidua capsularis
fuses with decidua parietalis
x When amniotic cavity grows even more, uterus begins to expand
x As amniotic cavity grows, so does the amount of amniotic fluid
x Membranes Æ amniochorionic mbrn, decidua capsularis
x Childbirth
o As uterine muscle contracts = increased pressure in amniotic fluid Æ membranes bulge
into cervical canal until ruptures and fluid flows out of vagina
o After child is delivered, decidua, membranes & placenta are all expelled
Amniotic Fluid
x Support for delicate tissues of growing embryo
x Allows for free movement & protection from external injury
x Avoids adhesion of fetus to amnion
x Full term = 1 L of amniotic fluid
x Hydramnios: too much amniotic fluid (over 1500 mL)
o Sometimes associated with atresia of esophagus – fetus can’t swallow amniotic fluid
x Oligamnios: too little fluid
o Sometimes assoc with renal agenesis Æ no urine added to amniotic fluid
x Both conditions cause complications during delivery and may cause abnormalities in fetus
x Constant exchange of water bt amniotic fluid & maternal blood Æ water replaced every 3 hrs
x 5th month Æ fetus begins to swallow fluid, absorbed thru gut Æ fetal blood Æ mother
x when fetal kidneys start working , passes urine into amniotic fluid
Timetable of Events in this Chapter
18

8 Trophoblast differentiates into cytotrophoblast & syncytiotrophoblast
9 Lacunae appear in syncytium
11 Embryo gets completely implanted in edometrium.
13 Primary villi formed
16 Secondary & tertiary villi are seen
2nd month Villi are seen all around trophoblast
4th month A definitive placenta is formed
Full term Placenta is shed about half an hour after birth of the baby
19
Embryology Dr. Drew Chapter 7

Formation of Tissues of the Body
x Epithelia from ectoderm, endoderm OR mesoderm

o Ectoderm Æ epithelia on external surfaces of body & terminal openings to outside
o Endoderm Æ epith lining gut & organs that develop as diverticula of gut
o Mesoderm Æ lining of UGT
x Mesenchyme = cartilage, bone, muscle, blood, & CTs
o BCs from bone marrow, liver, spleen
o Lymphocytes formed in lymphoid tissues
x Endochondral ossification: cartilage later replaced by bone
x Intramembranous ossification: direct ossification of membrane
x Center of Ossification: where ossification starts
o Diaphysis from primary ossification center
o Epiphyses from secondary ossification center (many at bone ends)
x Epiphyseal plate: separates diaphysis and epiphysis; made up of cartilage, growth in length here
x Somites Æ 3 divisions
o Dermatome Æ dermis
o Myotome Æ skeletal muscle
o Sclerotome Æ vertebral column & ribs
x Skeletal Muscle derived from somites & mesenchyme of region
x Smooth Muscle from mesenchyme related to viscera & blood vessels
x Cardiac Muscle from mesoderm related to developing heart
x Neurons & Neuroglial cells from neural tube
Epithelial Tissue: cells arranged like cont’s sheets; line external & internal surfaces of body & cavities
x Derived from ectoderm, endoderm or mesoderm
o Ectoderm Æ epithelia on external surfaces of body & terminal openings to outside
skin, hair follicles, sweat glands, sebaceous glands, mammary glands
epith over cornea & conjunctiva, ext aud meatus, outer tympanic mbrn
epith of some parts of mouth, lower anal canal, terminal parts of male urethra,
parts of female external genitalia
o Endoderm Æ lining gut & organs that dvl’p as diverticula of gut (ie: liver, pancreas)
Entire gut except ectoderm parts of mouth & anal canal
Auditory tube & middle ear
Respiratory tract
Part of urinary bladder, urethra & vagina
o Mesoderm Æ lining of UGT
Tubules of kidneys, ureter, trigone of urinary bladder
Uterine tubes, uterus, part of vagina
Testis & its duct system
Endothelium of heart, BVs & lymphatics
Mesothelium lining pericardial, peritoneal & pleural cavities & cavities of joints
Glands
x Develop as diverticula from epith surfaces
x Opening of duct usually where original outgrowth from deverticula occurs
o Endocrine Æ gland is not associated with epithelial origin
x Proximal part of diverticula become canalized Æ duct system

x Distal parts of diverticula Æ secretory elements
x Ectoderm Æ sweat glands, mammary glands
x Endoderm Æ pancreas, liver, posterior pituitary
x Mesoderm Æ adrenal cortex, anterior pituitary
x Mixed Æ prostate, pituitary
Mesenchyme
x Chondroblasts: form cartilage
x Osteoblasts: form bone
x Myoblasts: form muscle
x Lymphoblasts & haemocytoblasts: form various BCs
x Endothelial cells: form BVs & primitive heart tubes
x Remaining mesenchymal cells after formation of tissues Æ various types of CT
Connective Tissue (CT)

x Cells, fibers, ground substance
x Formation of Loose CT
o Mesenchymal Æ fibroblasts Æ secrete ground subst, synthesize collagen, reticular &
elastic fibers
x Some mesenchymal Æ Histiocytes, mast cells, plasma cells, fat cells
Formation of Blood
x Occurs before somites appear & continues throughout life
x 3rd week Æ formation of BVs & BCs seen in wall of yolk sac around allantoic diverticulum &
connecting stalk (clusters of mesodermal cells Æ blood islands)
o Mesodermal cells Æ precursor (haemangioblasts) = BVs & BCs
o Hematopoietic stem cells: formed in center of blood islands = precursor of all BCs
o Angioblasts: formed at periphery of islands = precursors of BVs
x Blood cells in yolk sac soon replaced by permanent stem cel;s from mesoderm around
developing aorta Æ form colonies in liver
x Late embryonic period Æ formation starts in liver
x Middle of prenatal life Æ definitive haematopoietic SCs from liver Æ colonize bone marrow;
x Birth Æ blood formation mainly in bone marrow; totipotent haemal stem cells Æ
pleuripotent haemal & lymphoid stem cells Æ colony forming units (CFU)
x Cells within 1 CFU are committed to diff into one specific line of blood cells Æ RBCs,
megakaryocytes, granulocytes, monocytes, macrophages, lymphocytes
o Erythrocytes: burst forming units (BFU) Æ CFU Æ RBCs
x Adult Æ bone marrow, lymph nodes, thymus, spleen
x Precursors of blood cells are mesodermal, but blood forming cells differentiating in relatin
ot wall of yolk sac & liver may be from endoderm
Formation of Cartilage
x Mesenchymal condensation: mesenchymal cells closely packed where cartilage to be formed
x Chondroblasts: rounded mesenchymal cells Æ form cartilage
o Influence intercellular substance of cartilage to be laid down
x Chondrocytes: chondroblasts that are trapped within intercellular substance
x Hyaline cartilage Æ collagen fibers present, but can’t see easily

x Fibrocartilage Æ many visible collagen fibers
x Elastic cartilage Æ intercell substance permeated by elastic fibers
x Perichondrium: fibrous mbrn around cartilage, formed by mesenchymal cells
Bone Formation (bone derived from mesoderm)

x Osteocytes: mature bone cells
x Osteoblasts: bone-forming cells; abundant in regions of bone formation
x Osteoclasts: bone-removing cells; seen in regions where bone is absorbed
x Intramembranous ossification: directly to bone (ie: skull, clavicle, mandible)
Endochondral ossification: cartilage Æ bone (ie: long bones)

1. Mesenchymal condensation at site of bone formation
2. Some mesenchymal cells become chondroblasts Æ hyaline cartilage Æ perichondrium
(vascular & contains osteogenic cells)
3. Enlargement of cells where bone formation is supposed to start
4. Calcification of intercellular subst bt enlarged cartilage cells by alkaline phosphatase;
primary areolae – empty spaces left behind when nutrition cut off to cell (= death)
5. BVs of periosteum with osteogenic cells (periosteal bud) invade calcified cartilaginous
matrix = wall of primary areolae Æ lg cavities secondary areolae
6. osteogenic cells become osteoblasts Æ around surfaces of plates of calcified cartilage
7. Osteoblasts lay down osteoid (layer of ossein fibrils embedded in gelatinous intercell matrix)
Æ calcified Æ lamellus of bone formed
8. Another layer of osteoid over 1st lamellus then over 2nd… Æ bony trabeculae formed
Center of ossifying cartilage is bone; as move away from center, see several layers:
x Region where cartilaginous matrix calcified & surround dead/dying cartilage cells
x Zone of hypertrophied cartilage cells in uncalcified matrix
x Normal cartilage with a lot of mitotic activity
Development of a Typical Long Bone

1. Mesenchymal condensation in limb bud region
2. mesenchymal condensation Æ cartilaginous model with perichondrium
3. Endochondral ossification starts in shaft Æ primary ossification center
4. Bone formation gradually extends towards ends of shaft – model lengthens
5. osteogenic cells in periosteum lay bone on surface of cartilaginous model via intramembranous
ossification Æ periosteal collar – gives strength to cartilage model in area of secondary areolae
6. Birth Æ bony diaphysis (shaft) w/ cartilaginous ends; 2ndary oss cntrs appear later in epiphysis
Growth of a Long Bone

x As more and more bone is formed on perosteal collar, osteoclasts reabsorb bone (ie: trabeculae)
from inside = marrow cavity (doesn’t reach epiphyseal plate)
x Most of bone from primary center removed except near ends Æ wall of shaft purely periosteal
bone formed by intramembranous ossification
x Layers of Epiphyseal Plate
o Zone of resting cartilage: cells are small, irregular arrangement
o Zone of proliferating cartilage: cells larger & undergo repeated mitosis; columns & ICM
o Zone of Calcification: cells larger & matrix becomes calcified
o Zone of dead cartilage cells Æ calcified Æ bone

o When bone has reached full length, cells stop proliferating
o Fusion of epiphysis: bone of diaphysis & epiphysis becomes continuous
x Metaphysis: between diaphysis & epiphyseal plate
o Region of active bone formation; highly vascular; no marrow cavity
o Calcium-turnover function of bone most active here
o Frequent site of infection
x Interstitial Growth: growth takes place by multiplication of cells (or increase of ICM)
o Tissue expands equally in all directions, shape maintained
x Appositional Growth: (ie: bone) growth only by deposition on surface or at ends
x Remodeling: removal of unwanted bone in order to give bone its proper shape
x Internal remodelling: arrangement of trabeculae of spongy bone and haversian systems of
compact bone change with change in stresses acting on bone
Anomalies of Bone Formation

x Dyschondroplasia or endochondromatosis: formation of irregular masses of cartilage w/in
metaphysic caused by excessive prolif of cartilage cells in epiphyseal plate or failure of normally
formed cartilage to be replaced by bone
x Exostosis: protrusion of abnormaml masses of bone formed in region of metaphysic
o Multiple exostosis or diaphyseal aclasis Æ result of interference w/ remodelling of ends
x Osteogenesis imperfecta: defective calcification of bone Æ multiple fractures
x Fibrous dysplasia: parts of bone replaced by fibrous tissue
x Osteosclerosis: bones have increased density (ie: osteopetrosis, marble bone disease)
x Achondroplasia: insufficient or disorderly formation of bone in region of epiphyseal cartilage;
person becomes dwarf; chondro-osteo-dystrophy Æ limbs fine but vertebral column stays short
x Cleido-cranial dysostosis: occurs in membranous bones; clavicle absent and deformities of skull
x Dwarfism: generalized underdevelopment
x Gigantism: generalized overdevelopment
x Asymmetric development: all bones of half of body affected
Fate of Somites
x Paraxial mesoderm segmented Æ somites Æ lie around neural tube
x Sclerotome: ventromedial; migrate medially Æ vertebral column & ribs
x Dermatome: lateral; migrate & line deep surface of ecto, cover whole body Æ dermis of skin to
subcutaneous tissue
x Myotome: intermediate Æ striated muscle
o Each myotome innervated by 1 spinal nerve in cervical to sacral regions
Number of somites formed = number of spinal nerves
o Coccygeal region Æ # somites > # spinal nerves; many degenerate
x Occipital somites: (4-5) Æ muscles of tongue, supplied by hypoglossal nerve
x Pre-occipital somites: supplied by CN III, IV, VI
Striated Muscle
x Derived from somites & mesenchyme
x Myotomes only give origin to musculature of trunk
x Occipital myotomes Æ tongue
x Pre-occipital Æ extrinsic muscles of eyeball
x Epimere: dorsal part of neck & trunk Æ muscles supplied by dorsal primary ramus
o Extensors of vertebral column (muscles of back)
x Hypomere: ventral part of neck & trunk Æ muscles supplied by ventral ramus
o Muscles of body wall and limbs
x In-situ from mesenchyme Æ Limb muscles develop in limb buds; ant muscles of abdominal &
thoracic walls
Smooth Muscle
x All smooth muscle derived from mesenchyme
x Splanchnopleuric mesoderm Æ walls of viscera (ie: stomach)
x Ectoderm Æ muscles of iris (sphincter & dilator pupillae) & myoepithelial cells of sweat glands
Cardiac Muscle
x Derived from splanchnoppleuric meso of developing heart tubes & pericardium
Formation of Neurons & Neuroglial Cells

x Formed in neural tube
x Matrix cell layer (aka: primitive ependymal or germinal layer): closest to lumen Æ neurons,
neuroglial cells, more germinal cells
x Mantle layer: developing neurons & neuroglial cells
x Marginal zone: no neurons; has reticulum formed by protoplasmic processes of developing
neuroglial cells (spongioblasts) Æ framework for growth of developing neurons in mantle layer
x Stages of Neuron Formation:
1. germinal cell Æ mantle = apolar neuroblast
2. 2 processes develop from apolar neuroblast Æ bipolar neuroblast
3. one process disappears Æ unipolar neuroblast
4. remaining process extends & smaller processes dvlp on opp side Æ multipolar neuroblast
5. main process grows Æ marginal layer = axon; lengthens and either stays in CNS or grows
out of CNS and becomes efferent nerve of PNS; est connections with other cell bodies or
dendrites or an effector organ (ie: muscle)
6. Smaller processes of neuroblast Æ dendrites Æ ramify & est connections w/ other neurons
7. Nissl granules appear Æ neurons lose ability to divide
x Neuroglial cells also formed from germinal cells of ependymal layer
o Glioblasts Æ mantle & marginal Æ medulloblasts (spongioblasts) Æ astroblasts Æ
astrocytes or oligodendroblasts Æ oligodendrocytes
x Microglia do NOT devlp frm neur tube – migrates into neural tube with BVs; mesodermal origin
x Neuroblasts complete differentiation and then neuroglia are formed
x Process begins during 4th month – not completed unto child is 2-3 yrs
x Nerve fibers become functional after they have acquired their myelin sheaths
x BVs of brain & surr CT derived from mesoderm – invade developing brain & spinal cord
x Pia mater & arachnoid mater from neural crest
x Dura mater from mesoderm surrounding neural crest
Formation of Myelin Sheath

x CNS Æ nerve fibers supported & ensheathed by neuroglial cells
x PNS Æ neurolemma Æ Schwann cells (from neural crest)
x Later in development, many nerve fibers of CNS & PNS develop myelin sheath
o CNS Æ derived from neuroglia (oligodendrocytes)
o PNS Æ derived from Schwann cells

x Each axon invaginates cyto of Schwann cell so that it is surrounded by the Schwann cell – cell
mbrn of Schwann cell also goes in = double-layered membrane Æ mesaxon
x Mesaxon elongates & spirally winds around axon, some fatty substances deposited bt layers
x Unmyelinated fibers Æ no elongation of mesaxon; several fibers invaginate same Schwann cell

The Skin & its Appendages
x Ectoderm Æ epidermis, nails, hair, sebaceous glands, mammary glands

o Sweat glands from epidermis
x Somites Æ dermis
Skin
x Epidermis from surface ectoderm
o Ectodermal cells prolif Æ stratified squamous epithelium
o Superficial layers shed off & mixed up with secretions of sebaceous glands = vernix
caseosa Æ covers skin of newborn for protection
o 3rd-5th months Æ epidermal ridges followed by characteristic patters (ie: fingerprints)
o Melanoblasts (dendritic cells) derived from neural crest Æ synthesize melanin pigments
responsible for skin & hair color
Albinism: absence of pigment in skin, hair & eyes because melanocytes can’t
synthesize melanin; autosomal recessive genetic condition
Vitiligo: similar but noncongenital; absence of pigment is patchy – degeneration
of existing melanocytes in affected areas; autoimmune disease
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o 8 -12 weeks Æ Cells of Merkel & of Langerhans appear in epidermis
x Dermis formed by condensation & differentiation of mesenchyme (derived from dermatome of
somite) under surface ectoderm
x Dermal Papillae: portions of dermis intervening bt projections of epidermis
x Aplasia: skin fails to develop in certain regions
x Dysplasia: skin may be abnormal in structure
o Congenital downgrowths of skin
o Maldevelopment of ectodermal derivatives (ie: hair, teeth, sweat & sebaceous glands)
Nails
x Develop from surface ectoderm
x Ectoderm at top of ea digit thickenedd Æ primary nail field Æ migrates onto dorsal aspect
o Skin of dorsal aspect of terminal part of digits supplied by nerves of ventral aspect
x Cells in most proximal part prolif Æ root of nail
o Cells of germinal layer multiply to form germinal matrix = thick layer of cells; these
multiply & transformed into nail substance Æ stratum lucidum of skin
x Anomychia: nails may be absent; occasionally show overdevelopment
Hair
x Derived from surface ectoderm
x Germinal layer of epidermis prolif Æ cylindrical mass grows into dermis at site of hair follicle
o Lower end becomes expanded & invaginated by condensation of meso Æ papilla
x Hair formed by prolif of germinal cells over papilla
x As grows twrds surface, cells forming wall of downgrowth surr hair Æ epithelial root sheath
x Dermal root sheath formed from surr mesenchymal cells
x Arrector pili: thin band of smooth muscle formed by meso cells Æ att to dermal root sheath
x Congenital alopecia: hair may be absent over scalp; eyebrows & eyelashes may be absent
x Atrichia: absence of hair in any part of the body
x Hypertrichosis: overgrowth of hair
Sebaceous Glands Æ each formed as a bud from ectodermal cells from wall of hair follicle
Sweat Glands
x Downgrowth from epidermis
x First solid then later canalized
x Lower end becomes coiled = secretory part of gland
Mammary Glands
x Situated along line that extends from axilla to inguinal region
x Ectoderm becomes thickened along line Æ mammary ridges, most of line disappears
x Each develops over part of line that is over pectoral region
x Thickened mass of epidermal cells project into dermis Æ 16-20 solid outgrowths arise and grow
into surrounding dermis Æ become canalized
x Secretory elements of gland are formed by proliferation of terminal parts of outgrowths
x Lactiferous duct formed at proximal end of each outgrowth
o Open into a pit formed by cavitation of the original epithelial thickening
o Growth of underlying mesoderm progressively pushes the wall of this pit outwards until
it becomes elevated above surface & forms nipple
x Males Æ remains rudimentary
x Females Æ ducts & secretory elements undergo extensive devl’t during puberty & pregnancy
x Amastia: gland may be absent on one or both sides
x Athelia: nipple may be absent
x Polythelia and polymastia: supernumerary nipples may be present anywhere along the milk line;
may remain rudimentary (polythelia) or may form accessory mammary glands (polymastia)
x Accessory breasts: may be found away from milk line in neck, cheeks, femoral triangle, vulva
x Inverted / crater nipple: nipple may fail to form resulting in lactiferous ducts opening into a pit
= difficulty suckling
x Micromastia: gland may be abnormally small
x Macromastia: gland may be abnormally large
x Gynaecomastia: male breat may enlarge like in females & may even secrete milk
Timetable of Events
7th week Mammary line established

8th week Melanoblasts start appearing
1st-3rd months Cells of neural crest migrate to skin
2nd month Surface ectoderm is single-layered
2nd-4th month surface ectoderm becomes multiple layered
3rd-4th month Dermal papillae are formed.

The Pharyngeal Arches
x Pharyngeal Arches: rod-like thickenings of mesoderm present in wall of foregut

x Originally 6 arches – 5th arch disappears
x Ventral ends of of arches of right & left sides meet in middle line in floor of pharynx
x Endoderm (lining pharynx) pushed outwards Æ series of pouches in interval bt any 2 arches
o Endodermal/pharyngeal pouches
x Skeletal element Æ cartilage Æ bone
x Striated muscle supplied by the nerve of the arch
x Arterial arch
x Meckel’s cartilage: cartilage of the 1st arch Æ incus & malleus of middle ear
x Cartilage of 2nd arch Æ stapes, styloid process, part of hyoid bone
x Cartilage of 3rd arch Æ greater part of hyoid bone
x Cartilages of 4th & 5th arches Æ cartilages of larynx
x Nerves of the pharyngeal arches
o 1st arch Æ Mandibular
o 2nd arch Æ Facial
o 3rd arch Æ Glossopharyngeal
o 4th arch Æ superior laryngeal
o 5th arch Æ recurrent laryngeal
x Muscles supplied by above nerves derived by mesoderm of arch
x External acoustic meatus: developed from 1st ectodermal cleft
x 1st endodermal pouch Æ Tubotympanic recess Æ Middle ear & auditory tube
x 2nd pouch Æ Palatine tonsil
x 3rd pouch Æ Inferior Parathyroid gland & thymus
x 4th pouch Æ superior parathyroid gland
x Thyroid gland from thyroglossal duct which is formed as a median diverticulum arising from the
floor of the pharynx (at forame caecum)
Structures formed in Mesoderm of each Arch

x Skeletal element Æ may remain cartilaginous or develop into bone
x Striated muscle: supplied by nerve of the arch; in later devl’t may or may not retain its att to
skeletal elements derived from the arch
o May subdivide to form a number of distinct muscles which may migrate away from
pharyngeal region Æ carry nerve w/ them (embryological origin determined by nerve)
x Arterial arch: ventral aorta (ventral to foregut); dorsal aorta (dorsal to foregut); series of
arterial arches connect ventral & dorsal aortae
o 1 in each pharyngeal arch
o Arrangedment of arteries become modified
x Each pharyngeal arch supplied by a nerve which supplies skeletal muscle of arch & sensory
branches to overlying ectoderm & endoderm
Derivatives of Skeletal Elements

x 1st arch Æ Meckel’s Cartilage Æ incus & malleus of middle ear at dorsal end
o Mandible surrounds ventral part of cartilage
o Perichondrium bt mandible & middle ear forms anterior ligament of malleus &
sphenomandibular ligament
1
o Mesenchyme Æ bones of face – maxilla, mandible, zygomatic, palatine, part of temporal

x 2nd arch
o Stapes
o Styloid process
o Stylohyoid ligament (from sheath)
o Smaller (lesser) cornu of hyoid bone
o Superior part of body of hyoid bone
x 3rd arch
o Greater cornu of hyoid bone
o Lower part of body of hyoid bone
x 4 & 6th arches Æ larynx (possible contribution from 5th arch)
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Nerves and Muscles of the Arches

x 1st arch Æ Mandibular Nerve
o Medial & lateral pterygoids, masseter, temporalis, mylohyoid, anterior belly of digastric,
tensor tympani, tensor palate
o Double nerve supply Æ mandibular (post-trematic), chorda tympani (pre-trematic) –
seen in anterior 2/3 of tongue (derived from ventral part of 1st arch
x 2nd arch Æ Facial Nerve
o Muscles of face, occipitofrontalis, platysma, stylohyoid, posterior belly of digastric,
stapedius, auricular muscles
x 3 arch Æ Glossopharyngeal
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o Stylopharyngeus
x 4 arch Æ Superior laryngeal
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o Muscles of larynx & pharynx

x 5 arch Æ Recurrent laryngeal
th
o Muscles of larynx & pharynx
Somitomeres
x 1 & 2 Æ muscles supplied by occulomotor nerve
x 3 Æ superior oblique muscle supplied by trochlear nerve
x 4 Æ muscles of 1st pharyngeal arch supplied by mandibular nerve
x 5 Æ lateral rectus supplied by abducent nerve
x 6 Æ muscles of 2nd pharyngeal arch supplied by facial nerve
x 7 Æ sylopharyngeus from 3rd supplied by glossopharyngeal nerve
x Occipital 1 & 2 Æ laryngeal muscles (from 4th & 6th) supplied by vagus
x Occipital 3 & 5 Æ muscles of tongue supplied by hypogloassal
Fate of Ectodermal Clefts

x After pharyngeal arches formed, neck region marked by series of groves or clefts on outside
x Dorsal part of 1st cleft bt 1st & 2nd arches Æ epithelial lining of external acoustic meatus; pinna
formed from series of hillocks on 1st & 2nd arches – adjoin first cleft;
x ventral part of first cleft obliterated
x cervical sinus: space bt overhanging 2nd arch and 3rd, 4th & 6th arches; lower overhanging border
of 2nd arch fuses with tissues caudal to arches Æ neck becomes smooth; cavity disappears
x branchial cysts: part of cavity of cervical sinus remains = swellings in neck along ant border of
sternocleidomastoid; usually right below angle of mandible
o branchial sinus: if cyst opens onto surface
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Fate of Endodermal Pouches

x 1st pouch
o Ventral Æ tongue
o Dorsal Æ receives contribution from dorsal part of 2nd pouch = tubotympanic recess
(diverticulum that grows towards region of developing ear)
x Proximal part of recess Æ auditory (pharyngotympanic) tube
x Distal part Æ middle ear cavity & tympanic antrum
x 2 pouch
nd
o Epithelium of ventral part Æ tonsil

o Dorsal Æ tubotympanic recess
x 3rd pouch
o Inferior parathyroid glands
o Thymus
x 4 pouch
th
o Superior parathyroid glands

o Thyroid gland
x 5th (Ultimobrnachial) Pouch
o Incorporated into 4th pouch Æ caudal pharyngeal complex Æ superior parathyroid
glands, parafollicular cells, thyroid gland
Development of Thymus
x Develops from endoderm of 3rd pharyngeal pouch
x Pouch cut off from pharyngeal wall & surface of ectoderm early in devl’t
x After separation from inferior parathyroid rudiment, each thymic rudiment has a thinner cranial
part & broader caudal part
o Thinner part Æ cervical part of thmus
o Broader parts of 2 sides Æ thorax Æ united by CT
x Endodermal cells invaded by vascular meso Æ many lymphoblasts Æ breaks of thymic tissue
into isolated masses = lobulated appearance
x Fragmentation of cervical part of thymus Æ accessory thymic tissue (from 4th pouch)
x Thymus increases in weight until puberty then gradually undergoes atrophy
Development of Parathyroid Glands

x Inferior parathyroid glands: from endoderm of 3rd pouch (parathyroid III)
o Closely related to thymus
o Carried caudally with thymus when descends into thorax; may descend into lower part of
neck or anterior mediastinum
x Superior parathyroid glands: from endoderm of 4th pouch (parathyroid IV)
o Prevented from descending bc close proximity to developing thyroid gland
x If remain at site of origin, can be seen near bifurcation of common carotid
Development of Thyroid Gland

x Develops mainly from thyroglossal duct
x Parafollicular cells derived from caudal pharyngeal complex (from 4th & 5th pouches)
x Tuberculum impar: midline swelling separating medial ends of 2 mandibular arches
x Epithelium of floor of pharynx thickens behind tuberculum in middle line Æ thyroglossal duct
x Foramen caecum: depression at site of origin of diverticulum
x 2 lobes arise form proliferation of bifid end of diverticulum in neck
3
x Fuses with caudal pharyngeal complex Æ parafollicular cells

x Pyramidal lobe: may arise from isthmus or one of the lobes; may have no connection with rest of
thyroid; may be divided into 2+ parts; could be a short stump or a long process reaching hyoid
x Isthmus may be absent
x One of the lobes of gland may be very small or absent
x Lingual Thyroid: lies under mucosa of dorsum of tongue = swelling Æ difficulty swallowing
x Intra-linguinal thyroid: embedded in muscular substance of tongue
x Suprahyoid thyroid: gland in midline of neck, above hyoid
x Infrahyoid thyroid: gland below hyoid, but above normal position
x Intrathoracic thyroid: entire or part of gland in thorax
x Ectopic Thyroid Tissue: thyroid tissue present outside of normal sites (ie: larynx, trachea,
esophagus, pons, pleura, pericardium & ovaries) Æ metastases in lymph nodes from carcinoma
of thyroid gland
x Thyroglossal cysts: may occur anywhere along course of duct; acquire 2ndary openings on
surface of neck = fistulae (opening at foramen caecum)
o Must remove all remnance of thyroglossal duct when removing cysts & fistulae
Timetable of Events
4th week (Day 22) Appearnace of 1st & 2nd arches

5th week (Day 29) 4 arches seen
Thyroid, parathyroid & thymus start forming
7th week thyroid gland reaches its definitive position
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The Skeleton
x Vertebral column from sclerotomes of somites

o Vertebra = segmented devl’t (fusion of sclerotomes)
o Intervertebral disc formed by middle of sclerotome
x Sternum Æ fusion of right & left sternal barts
x Skull from mesenchyme around brain (intramembranous bones)
x Mandible from mesenchyme of mandibular process
x Limb buds grow outward from side of embryo Æ devl’p into limbs
o Limb bones from mesenchyme of buds
o Joints formed between bone ends
Vertebral Column
x Formed from sclerotomes of somites
x Mesenchyme surrounds notochord and extends around neural tube; also extends laterally where
transverse processes will be and extends ventrally where ribs will be
x Perichordal Disc: middle region of segment of somite where mesenchymal cells are condensed;
develop into intervertebral disc
o Formation of interspinous & intertransverse ligaments same process
x Vertebral body formed when less condensed parts of segment fuse (cranial Æ caudal)
o Same process for neural arch, transverse processes & costal elements
x Each vertebra is made from parts of 2 somites
x Each intervertebral disc is made from 1 somite
x Transverse processes & ribs intersegmented separate muscles from 2 adjoining myotomes
x Spinal nerves come out between 2 vertebrae and lie in between 2 ribs
x BVs that supply myotome structures intersegmented Æ ICAs & lumbar arteries
x Mesenchyme converted to cartilage via centers of chondrification = cartilage model
x 3 Primary ossification centers per vertebra (1 per neural arch & 1 for body)
x Neurocentral joints: centrum (body) & neural arch joined by cartilage at birth
x Neurocentral line: junc’n bt centrum & neural arch after fusion
x Spina bifida: halves of neural arch don’t fuse in midline = gap bt neural arches
o Spina bifida occulta Æ gap is not obvious
o Meningocoele Æ bulging out of meninges through gap
o Meningomyelocoele Æ bulging out of meninges and neural elements through gap
o Ĺ$)3LQDPQLRWLFIOXLG
x Hemivertebra: only 2 primary ossification centers and 1 part doesn’t devl’p; usually assoc with
absence of corresponding rib
x Anterior spina bifida: 2 halves of vertebral body formed normally, but don’t fuse together = gap
o When gap is big enough, meninges & nerves bulge out
x Klippel-Feil Syndrome: fusion of 2+ vertebrae in cervical region
o Occipitalization of atlas: atlas fused to occipital bone
o Sacralization of 5th Lumbar Vertebra: L5 partially or completely fused to sacrum
x Lumbarization of 1st Sacral Vertebra: S1 is separate from rest of sacrum; odontoid process may
be separate from rest of axis vertebra
x Spondylolisthesia: L5 body slips fwrds over sacrum when don’t have both inf articular processes
x Diastematomylia: vertebral canal divided laterally by projected shelf of bone; spinal cord splites
into 2 longitudinally
1
x Chondro-osteo-dystrophy: defective ossification of vertebral bodies Æ short trunk, normal limbs

x Sacrococcygeal teratoma: tumor from cells of primitive knot att to lower end of spine
x Abnormalities in formation of vertebral column may cause:
o Congenital scoliosis: spine bent over itself
o Congential torticolis: cervical vertebral deformities Æ head tilted and rotated to opp side
o Too much pressure on Spinal nerves or cord Æ paralysis
o backache
Ribs
x Ventral extensions of sclerotomic mesenchyme that forms vertebral arches
x Thoracic Æ primitive costal arch Æ chondrification Æ ossification Æ “rib”
o Some mesenchyme near transverse process NOT ossified = costotransverse joint
x Cervical, lumbar & sacral Æ chondrification & ossification only near transverse process
o Costal element – bone fused to transverse process
The Sternum
x Fusion of 2 sternal bars/plates in midline (cranial Æ caudal)
x 7th week Æ mesenchymal condensations become cartilaginous
x Sternal bars continuous with ribs
x Manubrium and body ossified separately; xiphoid ossified later in life
x Hemivertebra Æ unilateral absence of a rib
x Accessory ribs: cervical rib (C7) or lumbar rib (L1)
x Sternal bars don’t fuse properly = midline cleft Æ bifid xiphoid process or midline foramina
x Funnel Chest: lower part of sternum & att ribs pushed in
o Central tendon of diaphragm abnormally short
o Less room for lungs to expand Æ respiratory difficulties
x Pigeon Chest: upper part of sternum & ribs project forwards
The Skull
x From mesenchyme around brain
x 4 occipital somites Æ base of skull & occipital bone
x otic & nasal capsules: mesenchymal condensations surr areas of internal ear & nose
o capsules also form mesenchymal basis of skull
x mandibular & maxillary processes formed as subdivisions of 2st branchial arch
x Bones Formed by Intramembranous Ossification
o Frontal & parietal
o Maxilla (not premaxilla), zygomatic & palatine (part of temporal)
o Nasal, lacrimal & vomer ossified in mbrn of nasal capsule
x Bones formed in Cartilage
o Ethmoid & inferior nasal conchae from cartilage of nasal capsule Æ NO ossification
x Bones formed partly in Cartilage and partly in Membrane
o Occipital: interparietal part formed in membrane, rest is endochondral ossification
o Sphenoid: lateral part of greater wing & pterygoid laminae in mbrn, rest is cartilage bone
o Temporal: squamous & tympanic parts formed in mbrn; petrous and mastoid part formed
by oss of cartilage of otic capsule; styloid process from cartilage of 2nd branchial arch
o Mandible: most formed in mbrn in mesenchyme of mandibular process; ventral part of
Meckel’s cartilage embedded in bone; condylar and coronoid processes are ossified from
secondary cartilages
2
x Anencephaly: greater part of vault of skull missing

x Cleidocranial dystosis: deformity to skull assoc with missing clavicle
x Scaphocephaly: sagittal suture unites too early Æ boat-shaped skull
x Acrocephaly: coronal suture unites too early Æ pointed skull
x Plagiocephaly: asymmetrical union of sutures Æ twisted skull
x Microcephaly: brain fails to grow and skull stays small
x Congenital hydrocephalus: cranial cavity expanse Æ separation of skull bones
x Hand-Schuller Christian disease: defect in reticuloendothelial sys; changes in bone secondary
x Occipital bone may be fused to atlas
x Mandibulo-facial dysostosis
Formation of Limbs
x Bones of limbs, shoulder & pelvic girdle from mesenchyme of limb buds via endochondral
ossification (clavical Æ intramembranous)
x 2nd month Æ limb buds arise from outgrowth from side-wall of embryo
x Limb buds Æ mass of mesenchyme covered by ectoderm
x Apical ectodermal ridge: thickened mass of ectoderm at tip of each limb bud
o Induces proliferation of mesenchyme cells and keep cells undifferentiated
o Areas away from ridge differentiate Æ cartilage, muscle…
x Forelimb buds appear earlier than hindlimb buds; as they grow they become subdivided by
constrictions into arm, forearm and hand
x Fingers and toes separated via interdigital cell death
x Mesenchymal cells form cartilaginous models of bones
x Preaxial (cranial) border Æ thumb & big toe
o Forearm Æ radius
o Leg Æ tibia
x Postaxial border
x Upper Limb Æ derived from part of body wall from segments C4-T2
o Innervated by corresponding spinal nerves
x Lower limb Æ form opposite to L2-S2
o rotated medially during development
o Ventral surface of limb represented by:
Inguinal region
Medial side of lower part of thigh
Popliteal surface of knee
Back of leg
Sole of foot
Joints
x From mesenchyme between ends of developing bones
x Differentiation into fibrous tissue Æ fibrous joint (syndesmosis)
x Cartilage Æ cartilaginous joint (synchondrosis or primary cartilaginous joints) Æ ossified
x site of synovial joint: mesenchyme in 3 layers
o 2 outer layers continuous w/ perichondrium on cartilaginous ends of articulating bones
o Middle layer becomes loose Æ forms cavity Æ lined by mesothelium Æ synovial mbrn
o Capsule and ligaments derived from surrounding mesenchyme
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Anomalies of Joints
x Phocomelia, Amelia: 1 or more limbs of body may be partially or completely absent; caused by
ingestion of harmful drugs
x Talipes equinovarus (club foot): foot shows marked plantar flexion & inversion
x Congenital strictures, congenital amputations, congenital contractures
x Syndactyly: abnormal fusion (bony or fibrous) bt adjoining digits
x Symphalangia: phalanges of a digit may be fused to one another
x Macrodactyly: digit abnormally large
x Brachydactyly: digit abnormally short
x Arachnodactyly: fingers long and thin – spider fingers
x Polydactyly: supernumerary digits; extra phalanx on thumb most common
x Lobster claw: palm or sole may show a deep longitudinal cleft
x Achondroplasia: limbs may remain short
x Congenital dysplasia: ends of bone imperfectly formed
x Congenital dislocation: hip joint most commonly affected
Timetable of Events
4th week (Day 26) Forelimb bud appears

4th week (Day 28) Hindlimb bud appears
5th week Limbs become paddle shaped

6th week (Day 36) Formation of future digits can be seen
Cartilaginous models of bone start forming
7th week Rotation of limbs occurs
8th week (Day 50) The elbow and knee are established, fingers & toes are free
Primary ossification centers are seen in many bones
12th week Primary ossification centers are seen in all long bones
Extermities most susceptible to teratogens during 4th–7th weeks; slightly less susceptible in 8th wk
4

Face, Nose and Palate
x Face derived from

o The frontonasal process
o First pharyngeal arch (mandibular arch) of each side
x Arch gives off a bud from its dorsal end Æ Maxillary process
o Maxillary process – grows ventro-medially cranial to the main part of the arch
o Now known as mandibular arch
x Ectoderm overlying the frontonasal process thickens bilaterally Æ Nasal Placodes
o Situated above the stomatodaeum
o Formation of placodes Æ underlying forebrain
o Placodes soon sink below the surface Æ nasal pits
Development of Lower Lip
x Mandibular processes of two sides grow towards each other Æ Fuse in the midline
x This fusion of the mandibular process forms – lower margin of the stomatodaeum
x Fused mandibular process gives rise to the lower lip, and to the lower jaw and mouth
Upper Lip
x Maxillary process grows medially, fuses w/ lat nasal process then w/ medial nasal proc.
x The medial and lateral nasal process both fuse with eo Æ Nasal pits = external nares
x Frontonasal process becomes narrower from side to side = exte nares coming closer to eo
x Upper lip (mesodermal basis of the lateral part of the lip) itself formed from max process.
x Overlying skin – derived from ectoderm
x Philtrum: Mesodermal basis of the median part of lip; from the frontonasal process
x Ectoderm from maxillary process overgrows this mesoderm to meet that of the opposite
maxillary process in the midline
x Skin of the entire upper lip is innervated by the maxillary nerves
x Muscles of the face and lips – from the meso of the 2nd branchial arch Æ Facial Nerve
Nose
x From the frontonasal & the medial and lateral nasal processes of the right and left sides
x External nare – nasal pits cut off from the stomatodaeum Æ fusion of maxillary process with the
medial nasal process
x External nares usually approach one another
x Frontonasal process becomes narrower and deeper part = nasal septum
x Prominence of nose ÆMesoderm heaps up in the median plane
x Forehead: groove bt regions of nose and bulging forebrain
x As nose becomes prominent – external nares come to open downwards instead of fwrds
x External form of the nose is established as such
Cheeks
x As the upper lip and lower lips are formed the stomatodaeum can be called the mouth
x Mouth – very broad
x Lateral part of mouth – bounded by the maxillary process
1
x Below – mandibular process

x Maxillary process and mandibular process fuse Æ cheeks
x Naso-optic furrow (nasolacrimal sulcus): fusion from the stomatodaeum to the medial angle of
the developing eye
x Nasolacrimal duct: a strip of ectoderm which becomes buried along the furrow
Eye
x First – ectodermal thickening
x Lens placode: on the ventro-lateral side of the developing forebrain
o sinks below the surface – cuts off from the surface of the ectoderm
x Developing eye – bulge out (directed laterally at first)
x Eye lids – derived from folds of ectoderm
o Ectoderm above and below the eyes
o Mesoderm enclosed within the folds
External Ear (Pinna)

x Formed around the dorsal part of the first ectodermal cleft
x Series of mesodermal thickenings on the 1st & 2nd arches where they adjoin the cleft
x Pinna – formed by the fusion of these thickenings
o When pinna first formed – lies caudal to the developing jaw
Pushed upwards & backwards into position when the mandibular process enlarges
If the mandibular process does NOT enlarge Æ ears remain low down
Development of Nasal Cavities

x formed by extension of the nasal pits
x Initially – pits have open communication with the stomatodaeum
x Soon – medial and lateral nasal processes fuse and form a partition bt the pit and stomatodaeum
x Primitive plate from frontonasal process
o fusion of the lateral nasal process and medial nasal process
o partition between the stomatodaeum and the nasal pit
x Nasal pits deepen to form the nasal sacs Æ expand both dorsally and caudally
x Dorsal sac is separated from stomatodaeum by bucconasal membrane Æ soon breaks down
x Anterior or external nares: ventral orifice of the nasal sac that opens on the face
x Primitive posterior nasal aperture: dorsal orifice that opens into the stomatodaeum
x Nasal Septum: the intervening tissue which becomes much thinned while narrowing of the
frontonasal process, the enlargement of the nasal cavities themselves, bring them closer together
x Lateral wall of nose – derived on each side from the lateral nasal process
x Nasal conchae: elevations on the lateral wall of each nasal cavity
x Original olfactory placodes – form olfactory epithelium
Anomalies of the Nasal Cavity

x Atresia of the cavity at external nares: at the posterior nasal aperture or in the cavity proper
o Unilateral or bilateral
o Very rarely – total absence of the nasal passages
x Congenital defects in the cribriform plate of the ethmoid Æ comm. bt cranial cavity and nose
x Nasal septum – may not be in the midline; may be deflected to one side or may be absent
x Nasal Cavity may communicate with the mouth
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Paranasal Sinuses
x Appear from the dverticula from the nasal cavity
x Maxillary and sphenoidal sinuses begin to develop before birth
o Other sinuses develop after birth
x Paranasal sinuses enlarge with the overall enlargement of the facial skeleton, including the jaws
Development of the Palate

x Maxillary process Æ upper lip & extends backwards on either side of the stomatodaeum
x Palatal process: a plate like shelf from each maxillary process grows medially
x Palate forms from the two palatal processes
x The primitive palate formed from the frontonasal process
x Definitive palate is formed by the fusion of
o Each palatal process with the posterior margin of the primitive palate
o Two palatal processes with each other in the midline (anterior Æ posterior)
o The medial edges of the palatal processes fuse with the free lower edge of the nasal
septum Æ separates the two nasal cavities from each other and from the mouth
x Mesoderm in the palate
o Undergoes intramembranous ossification Æ hard palate
o Ossification does NOT extend into the most posterior portion Æ soft palate
o Part of the palate derived from the frontonasal process = premaxilla
o Premaxilla carries the incisor teeth
x Cleft Palate: caused by defective fusion of the various components of the
o Clefts of the palate that extend to its anterior end – associated with harelip
o Fusion of the maxillary process with teh frontonasal process = upper lip & palate
o result in anomalous communications between the mouth and the nose
o unilateral or bilateral
3

Alimentary System I: Mouth, Pharynx & Related Structures
x Ectoderm
o Ameloblasts Æ enamel
x Mesoderm (from neural crest)
o Odontoblasts Æ dentin
x Mesenchyme around tooth
o Cementum
o Periodontal ligament
Mouth
x From stomatodaeum and foregut Æ epithelial lining is partly ectoderm & partly endoderm
x Epithelium on inside of lips, cheeks & palate, teeth & gums Æ ectoderm
x Epithelium of tongue Æ endoderm
x Roof of mouth formed by palate (Ch. 11)
o Labio-gingival furrow: separates alveolar process of upper jaw from upper lip & cheek
x Floor of mouth Æ mandibular processes form:
o Tongue
Linguo-gingival sulcus laterally separates mandibular process & swelling
o Lower lip & lower part of cheeks
Labio-gingival sulcus forms between mand process & linguo-gingival sulcus
x Quickly deepens and tissues of mand arch (lateral) form lower lip (cheek)
o Lower jaw
Alveolar Process: elevation that forms bt 2 sulci as they deepen Æ jaw & teeth
Teeth
x Formed in alveolar process
x Dental lamina: thickened portion of epith on tip of process Æ goes into mesoderm
x Enamel organ: Series of local thickenings with dental lamina Æ each forms 1 milk tooth (5 on
each alveolar process)
x Formation of Enamel Organ & Devl’t of Tooth:
1. Enamel organ (EO) formed by localized proliferation of cells of dental lamina
2. Cap Stage: tooth germ (dermal papilla + EO) looks like a cap
a. Dermal papilla: cup-shaped downgrowth of EO w/ mesenc cells (from neural crest)
3. Ameloblasts: columnar cells of enamel organ that line the papilla
4. Bell Stage: developing tooth looks like a bell
a. Odontoblasts: mesodermal cells adjacent to ameloblasts, arranged as a continuous
layer (separated from ameloblasts via BM)
b. Pulp formed by remaining cells of papilla
5. Ameloblasts lay down enamel on superficial (outer) surface of BM;
Odontoblasts lay down dentine on deeper surface of BM
As each lay down more layers – the amelo & odonto layers grow farther and farther apart
6. Dental cuticle: thin mbrn over enamel after it has fully formed and ameloblasts disappear
Odontoblasts continue to separate dentin from the pulp throughout life of the tooth
7. Ossification of the alveolar processes Æ roots of teeth become surrounded by bone
x Root est by continued growth into underlying mesenchyme
1
o As layers of dentin deposited, pulp space becomes narrower Æ gradually becomes canal
through which nerves & blood vessels pass
o No ameloblasts in this region
o Cementoblasts derived from mesenchymal cells around dentin Æ lay down cementum
o Periodontal ligament formed by mesenchymal cells; connects root to socket in jaw bone
x Formation of Permanent Teeth
o Dental lamina gives off series of buds on medial side of each developing milk tooth,
which form enamel organs just like above Æ permanent incisors, canines & premolars
o Buds from dental lamina, posterior to region of last milk tooth = permanent molars
x Dental lamina formed during 6TH WEEK
x Before Birth Æ all temp teeth & permanent lower 1st molar begin to calcify
x Birth Æ germs of all temp teeth & permanent incisors, canines & 1st molars most devlp’d; germs
of perm premolars & 2nd molars are rudimentary
x After Birth Æ formation of 3rd molar & other permanent teeth begin to calcify at varying ages
x Eruption of a tooth is preceded by a major devlp’t of its root; erupt at varying ages
o Temporary or Milk Teeth
6-9 mo Æ Lower central incisor
8-10 mo Æ Upper incisors
12-20 mo Æ Lower lateral incisors & First molar
16-20 mo Æ Canines
20-39 mo Æ Second molars
o Permanent Teeth
6-7 yrs Æ first molar
6-8 yrs Æ central incisors
7-9 yrs Æ lateral incisors
10-12 yrs Æ premolars & canines
11-13 yrs Æ second molars
17-21 yrs Æ third molars
x Anomalies of Teeth
o Anodentia: complete absence of 1+ teeth
o Supernumerary teeth may be present
o Individual teeth may be abnormal (ie: too big/small, too many cusps or roots)
o Germination: 2+ teeth fused together
o Malocclusion: incorrect alignment of upper & lower teeth; may be caused by 1 or more
of the anomalies above or defects of the jaws
o Teeth may erupt too early (ie: lower incisors present at birth)
o Eruption of teeth delayed (ie: 3rd molar may not even develop)
o Teeth may form in abnormal situations (ie: in ovary or in hypophysis cerebri)
o Improper formation of enamel or dentin of tooth
Tongue Æ 4TH WEEK

x Lingual swellings formed by proliferation of medial-most parts of mandibular arches
x Tuberculum impar: swelling in midline Æ partially separates lingual swellings
o Thyroglossal duct formed by downgrowth from epith right behind (=foramen caecum)
x Hypo-branchial eminence: midline swellings in relation to 2nd, 3rd, & 4th arches
o Cranial division (2nd & 3rd arch) Æ copula
o Caudal division (4th arch) Æ epiglottis
x 1st ARCH Æ Ant 2/3 of tongue formed by fusion of tuberculum impar & 2 lingual swellings
2
o Supplied by lingual branch of mandibular nerve (post-trematic nerve of 1st arch) &
chorda tympani of facial nerve (pre-trematic nerve of 1st arch)
x 3RD ARCH Æ Post 1/3 of tongue from cranial part of hypobranchial eminence (3rd arch grows
over 2nd and fuses with mesoderm of 1st arch)
o Supplied by glossopharyngeal nerve
x TH
4 ARCH Æ Posterior-most part of tongue
o Supplied by superior laryngeal nerve
x Musculature of the tongue from occipital myotomes (hypoglossal is nerve for these myotomes)
x Epithelium of tongue
o First made of a single layer of cells which later becomes stratified and papillae appear
o Taste buds formed in relation to terminal branches of innervating nerve fibers
x Anomalies of the Tongue
o Macroglossia: tongue too large
o Microglossia: tongue too small
o Aglossia: tongue absent (very rare)
o Tongue may be bifid bc 2 lingual swellings did not fuse
o Ankyloglossia (aka Tong-tie): apicle part of tongue anchored to floor of mouth by
overdeveloped frenulum; interferes with speech
Ankyloglossia superior: tongue adherent to palate
o Persistence of tuberculum impar Æ red, rhomboid-shaped smooth zone on tongue in front
of foramen caecum can be seen
o Thyroid tissue may be present in tongue either under mucosa or within muscles
o Remnants of thyroglossal duct may form cysts at base of tongue
o Surface of tongue may show fissures
Salivary Glands
x Devl’p as outgrowths of buccal epithelium; first solid then become canalized
x Branch repeatedly to form duct system; terminal parts Æ secretory acini
x Devl’p near junctional area bt ectoderm of stomatodaeum & endoderm of forgut (can’t tell
whether they are of ecto or endo origin)
x Submandibular & sublingual glands from linguo-gingival sulcus therefore endodermal
x 1+ salivary glands may sometimes be absent
Tonsils
x Palatine tonsil develops in relation to lateral part of 2nd POUCH
o Endodermal lining undergoes considerable proliferation
o Invades underlying mesoderm of 2nd arch Æ tonsillar stroma
o Most of pouch obliterated (Intratonsillar cleft/tonsillar fossa = persisting part of pouch)
o Lymphocyte collect in tonsillar stroma under epithelium (could have differentiated in situ
or derived from blood or from liver as lymphoblasts)
x Tubal tonsils, lingual tonsils & pharyngeal tonsils develop similarly
Pharynx
x Derived from cranial-most part of foregut
x Most of endodermal pouches lose contact with pharyngeal wall
x Opening of pharyngo-tympanic tube = site of origin of tubotympanic recess
x Inlet of larynx = Site of midline respiratory diverticulum
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x Pharynx subdivides with establishment of palate & mouth Æ nasopharynx, oropharynx,

laryngopharynx
x Muscles forming wall of pharynx derived from 3rd & subsequent pharyngeal arches
Timetable of Events
Age Developmental Events

4 weeks Tongue starts forming (ie: 2 lateral lingual swellings & tuberculum impar visible)
5 weeks Hypobranchial eminence becomes visible
6 weeks Dental laminae of upper & lower jaws established
7 weeks Salivary glands start developing
8 weeks Enamel organs formed
10 weeks enamel organ becomes cup-shaped (Cap Stage)
3 months Formation of tonsil begins
5 months Tonsil is infiltrated by lymphatic tissue
6 months Enamel & dentin have formed considerably
Tongue formation is almost complete
Just before birth Cementum formed
After birth Periodontal ligaments are formed before eruption of teeth
4

Alimentary System II: Gastrointestinal Tract
x Epithelial lining of GIT from endoderm

x Epithelium surrounding region of mouth from ectoderm of somatodaem
x Epith of anal canal Æ ectoderm of proctodaeum
x Part of yolk sac w/in head & tail folds Æ primitive gut in free commu w/ rest of yolk sac
o Foregut Æ cranial to prim gut; separated frm stomatodaeum by buccopharyngeal mrn
o Hindgut Æ caudal to prim gut; separated from proctodaeum by cloacal membrane
o Midgut is in between
o Both membranes disappear so gut is open to exterior on both ends
x Midline artery Æ dorsal aorta lies dorsal and gives off branches to the gut
o Vitelline arteries Æ in area of midgut, initially run right up to yolk sac
o Most of the ventral branches disappear and only three remain:
Celiac A Æ foregut
Superior Mesenteric A Æ midgut
Inferior Mesenteric A Æ hindgut
x Communication btw midgut and yolk sac narrows Æ midgut become tubular Æ forms a loop
o Superior mesenteric A runs to apex of loop, divides loop
Proximal/prearterial segment
Distal/postarterial segment
x Caecal bud Æ arises from postarterial segment near apex of loop
x Midgut loop outside abd cavity Æ thru umbilical opening Æ e-e coelom (proxmal part of cord)
Æ loop to abdominal cavity
x Allantoic Diverticulum: opens into ventral part of hindgut
x Cloaca: part of hindgut that is caudal to attachment of allantoic diverticulum
o Urorectal septum: divides cloaca, formed in the angle btw allantois and the cloaca
Primitive UG sinus: ventral division, broad Æ UG system
Primitive Rectum: dorsal division, narrow Æ rectum & part of anal canal
o Urorectal septum grows towards cloacal membrane and fuses with it
Urogenital membrane Æ ventral part, related to urogenital sinus
Anal membrane Æ dorsal part, related to rectum
x Mesoderm lies at the bottom of anal pit (proctodaeum) Æ anal canal
Derivatives of Foregut
x Part of the floor of mouth, incl. tongue x Duodenum Æ 1st part & superior half of
x Pharynx 2nd part (up to major duodenal papilla)
x Various derivatives of the pharyngeal x Liver and extra-hepatic biliary system
pouches, and the thyroid x Pancreas
x Esophagus x Respiratory system
x Stomach
Derivatives of Midgut
x Duodenum Æ inferior half of 2nd part x Caecum and appendix
(distal to papilla), 3rd part, 4th part x Ascending colon
x Jejunum x Right ҀRIWUDnsverse colon
x Ileum
1
Derivatives of Hindgut
x Left ѿRIWUDQVYHUVHFRORQ x Upper part of anal canal
x Descending and pelvic colon x Parts of the urogenital system derived
x Rectum from the primitive urogenital sinus
Endoderm of foregut, midgut, and hindgut Æ epithelial lining of intestinal tract

Splanchnopleuric mesoderm Æ sm muscle, CT & peritoneum
Esophagus Æ FOREGUT
x Bt pharynx and stomach
x Elongates as the neck forms (w/ descent of the diaphragm and enlargement of pleural cavities)
x Musculature derived from mesenchyme surrounding foregut
o Upper Ҁ mesenchyme forms striated muscle
o Lower ѿ mesenchyme forms smooth muscle (same as rest of gut)
Stomach
x First seen as a fusiform dilatation of the foregut Æ distal to oesophagus
x Dorsal mesogastrium Æ fold of peritoneum that att. dorsal border w/ post. abdominal wall
o Gastropleuric lig Æ part of dorsal mesogastrium bt spleen & stomach
o Lienorenal ligament Æ part bt spleen & posterior abdominal wall
x Ventral mesogastrium Æ fold that attaches ventral border to septum transversum
o Septum transversum Æ liver & diaphragm
o Lesser omentum Æ part of ventral mesogastrium bt liver and stomach
o Coronary & Falciform Ligaments Æ part bt liver & diaphragm (& ant abdominal wall)
x Lesser curvature Æ ventral border now faces upward and to the left
x Greater curvature Æ dorsal border now points downward and to the left
x Rotation and growth
o left surface Æ Anterior
o right surface Æ Posterior
Duodenum
x Foregut Æ 1st part + superior half of 2nd part
x Midgut Æ lower half of 2nd part + 3rd part + 4th part
x Mesoduodenum Æ a mesentery that connects loop of duodenum to post. abdominal wall
o Fuses with peritoneum of prost. abdominal wall when loop falls to the right
o Duodenum becomes retroperitoneal
o Small part persist btw duodenum and pylorus Æ duodenal cap (in radiographs)
x Post. part of duodenum supplied by branches of celiac artery
x Distal part of duodenum supplied by branches of superior mesenteric
Jejunum and Ileum

x Jejunum Æ from Prearterial segment of midgut loop
x Terminal part of ileum Æ from postarterial segment proximal to caecal bud
Caecum and Appendix

x Formed from the enlargement of the caecal bud (diverticulum of postarterial segment)
o Proximal part grows rapidly Æcaecum
2
o Distal part stays narrow Æ appendix

x Lateral wall of caecum grows faster Æ appendix moves from apex of caecum to medial wall
Ascending Colon Æ Develops from postarterial segment of midgut loop that is distal to caecal bud
Transverse Colon
x Right Ҁ develop from postarterial segment Æ superior mesenteric artery
x Left ѿDULVHVIURPKLQGJXWÆ inferior mesenteric artery
Descending Colon Æ Develops from hindgut
Rectum Æ from primitive rectum (dorsal part of cloaca); upper part from hindgut (prox cloaca)
Anal Canal
x Endoderm (primitive rectum) & Ectoderm (anal pit/proctodaeum)
x Pectinate line (anal valves): junction bt endoderm & ectoderm
Rotation of the Gut

x Midgut loop outside abd cavity in e-e coelom near umbilicus
x initially lies in sagittal plane Æ Proximal segment cranial and ventral to distal segment
x Steps of Rotation:
1. Ventral view Æ anticlockwise 4 by 90o Æ loop is now in horizontal plane
a. Prearterial segment lies on right side
b. Postarterial segment on left side
2. Prearterial segment Ĺ in length = coils of jejunum & ileum Æ right side of distal limb
3. Prearterial segment (jejunum and ileum) return to abdominal cavity Æ anticlockwise 4
a. Jejunum and ileum pass behind superior mesenteric A in left half of abdomen;
b. Duodenum behind sup mesenteric A
c. Jejunem & ileum occupy the posterior and left part of abdominal cavity
4. Postarterial segment returns to abdominal cavity Æ undergoes anticlockwise 4
a. Transverse colon anterior. to superior mesenteric A Æ caecum on the right side
5. Caecum lies just below the liver Æ ascending colon cannot be demarcated
a. Caecum gradually descends to iliac fossa Æ regions of colon become distinct
x Non-rotation of the midgut loop Æ SI lies toward right side of the abd cavity and LI twrds left
x Reversed rotation Æ transverse colon crosses behind sup mes A & duodenum goes in front
x Non-return of umbilical hernia
o Exomphalos/omphalocoele: coils of midgut loop don’t return to abd cavity, intestines are
hanging out the umbilicus covered only by amnion
o Congenital umbilical hernia: loops of intestines & other abd contents seen outside
muscle layer & skin absent in the region of the umbilicus = defect in abdominal
wall where contents can pass through Æ covered w/ peritoneum
Fixation of the Gut

x At first all parts SI & LI att. to posterior abdominal wall by a mesentery
x After rotation Æ duodenum, ascending & descending colon, and rectum Æ retroperitoneal
o Fusion of mesenteries with posterior abdominal wall
o Mesentery of the small intestine, transverse mesocolon, and pelvic mesocolon persist
3
x Parts of the intestine that are normally retroperitoneal may have a mesentery.
o Volvulus: abnormal mobility of these parts = twisting
Twisting of BVs to the loop = obstruction of blood supply
x Parts of the intestines that normally have mesentery fixed by abnormal adhesions of peritoneum
x Caecum may remain sub-hepatic or descend only to the lumbar region or descend into the pelvis
Congenital Obstruction
x Atresia Æ continuity of the lumen of the gut is interfered with:
o segment of gut may be missing
o segment of the gut may be replaced by fibrous tissue
o septum may block the lumen
x Stenosis Æ lumen may be abnormally narrow
o During early devl’t, lumen undergoes epithelial occlusion, then later recanalize
o Some cases of atresia, duplication and stenosis due to abnormal recanalization
x Non-development of nerve plexuses in the wall of a part of the intestinal tract
o difficulty in the passage of intestinal contents through the part
o Megacolon/Hirschsprung’s Disease Æ part of colon proximal to defective segment
becomes greatly distended with its contents
x Abnormal thickening of muscular wall Æ typically seen at pyloric end of the stomach
(congenital pyloric stenosis), the thickened muscle bulges into the lumen and narrows it
x External pressure by abnormal peritoneal bands or abnormal BVs Æ often seen in relation to
the duodenum which can also be compressed by an annular pancreas
x Imperforate Anus Æ stenosis or atresia of the lower part of the rectum or the anal canal
Abnormal Communications or Fistulae

x Gut may have abnormal communications with other cavities or with the surface of the body
x seen mostly with the esophagus and the rectum and usually assoc with atresia of normal passage
o Tracheo-esophageal fistula Æ atresia of esoph = abnormal comm bt esoph & trachea
o Incomplete septation of the cloaca Æ rectum may comm w/ urinary bladder, urethra, or
vagina or may open onto the perineum at abnormal site, assoc with imperforate anus
Duplication
x Varying lengths of the intestinal tract may be duplicated
x Duplicate part may = small cyst or may be very long
x May or may not communicate w/ the rest of the intestine
Diverticula
x May arise from any part of gut, but most common near the duodenum
x Meckel’s diverticulum/diverticulum ilei Æ persistence of part of vitello-intestinal duct =
diverticulum at terminal part of the ileum
o may undergo inflammation Æ symptoms related to appendicitis
o pancreatic tiss or gastric type mucosa may be in its wall Æ ulceration or perforation
o fecal fistula at umbilicus Æ all of the vitello-intestinal duct present
o umbilical sinus Æ only the distal part of vitello-intestinal duct present
o enterocystoma/vitelline cyst Æ vitello-intestinal duct rep by cysts or fibrous cords
fibrous cords = danger later; coils of intestine may get twisted = strangulation
remnants of v-i duct may also give rise to growths
4
Situs Inversus
x All abdominal and thoracic viscera are laterally transposed
x All parts that are normally on the right side are seen on the left and vice versa
o Appendix and duodenum lie on the left side and the stomach on the right side
Timetable of Events

16 days Allontoic diverticulum starts appearing
3 weeks Gut begins to acquire tubular form bc head and tail folds
At the end of 3rd week the buccopharyngeal membrane ruptures
4 weeks The fusiform shape of the stomach becomes visible
5 weeks Stomach rotates and dilates and intestinal loop begins to form
Caecal bud can be identified
6 weeks Intestinal loop is well formed
Urorectal septum starts dividing the cloaca
Allantois and appendix become clearly visible
Stomach completes its rotation
7 weeks Septation of cloaca into rectum and urogenital sinus is completed
Intestinal loop herniates out of the abdominal cavity
8 weeks Intestinal loop rotates counterclockwise
9 weeks Anal membrane breaks down
3 months Head and tail folds are completed
Herniated coils of intestine return to the abdominal cavity
5

Liver, Pancreas, Spleen; Respiratory System; Body Cavities
x Hepatic bud: arries from gut at junction of foregut & midgut

o Liver & biliary passages (endoderm) derived from here
x Pancreas (endoderm) from 2 buds that arise from gut near junction of foregut & midgut
o Dorsal bud Æ most of pancreas
o Ventral bud Æ part of head of pancreas
x Spleen (mesoderm) develops in mesogastrium
x Respiratory system from median diverticulum of foregut (endoderm)
o Cranial end Æ larynx & trachea
o Caudal end Æ Right & left lung buds
Repeated division of lung buds = bronchial tree & alveoli of lungs
x Pericardial cavity from median midline part of i-e coelom
o After head fold Æ lies ventral to foregut
x Periotneal cavity from R & L limbs of i-e coelom
o After formation of lateral folds of embryonic disc Æ 2 limbs unite = 1 cavity
x Pleural Cavities from R & L pericardio-peritoneal canals
o Each canal invaginated by corresponding lung bud
o Enlargement of bud = great enlargement of canal & formation of pleural cavity
x Diaphragm develops in relation to septum transversum
o Receives contribution from pleuro-peritoneal mbrns, body wall & mesenteries of esoph
Liver
x From endodermal bud from ventral aspect of gut @ junc’n bt foregut & midgut
x Bud grows & passes into ventral mesogastrium Æ septum transversum Æ enlarges & divides
o Pars hepatica: larger, cranial part Æ right & left parts = lobes of liver
R & L divisions grow & extend into septum transversum; cells broken up into
interlacing columns – hepatic trabeculae
Sinusoids from umbilical & vitelline veins & mesenchym of septum transversum
o Pars cystica: smaller, caudal part = gall bladder & cystic duct
x Parenchyma of liver & bile capillaries from endodermal cells of hepatic bud
x Capsule & fibrous tissue basis from mesoderm of septum transversum
x Fetal liver = center of hemopoiesis
o Large aggregations of blood-forming cells present bt hepatic cells & BVs
x 3 months Æ Bile formation begins = black color of first stools (meconium) of newborn
x Rudimentary left lobe
x Anomalous lobation
x Reidel’s Lobe
x Absence of quadrate lobe w/ absence of gall bladder
x Accessory liver in falciform ligament
Gall Bladder & Biliary Passages

x From pars cystica of hepatic bud
x Bile duct froms in part of hepatic bud that is proximal to pars cystica
o First opens on ventral side of developing duodenum
o After rotation of duodenal loop; opens on dorsomedial aspect w/ ventral pancreatic bud
1
x Anomalies of Shape
o Phygian cap: cap-like structure that results when fundus folded on itself
o Hartmann’s pouch: wall of infundibulum may project downwards as a pouch
May be adherent to cystic duct or even bile duct
x Anomalies of Position
o Organ lies transversely on under-surface of right lobe of liver; or under left lobe
o Floating Gall Bladder: gall bladder may be lined by peritoneum on all sides
may be att to liver by a fold of peritoneum or may be completely free
o Gall bladder may be embedded in substance of the liver
x Duplication
o Lumen partially or completely subdivided by a septum that night extend into cystic duct
o Gall bladder may be partially or completely duplicated
x Sessile bladder: GB may open directly into bilde duct
x Gall bladder may be absent
x Diverticula may arise from any part of the organ
Pancreas
x From dorsal & ventral endodermal buds that arise from part of gut that will = 2nd part of duod
x Ventral bud Æ close to hepatic bud in inferior angle bt it and duodenum
x Dorsal bud Æ frm dorsal aspect of gut & grows into mesoduodenum & dorsal mesogastrium
x When duodenal loop falls to the right, ventral bud points right & dorsal bud points left
x Differential growth of wall of gut, att of ventral bud (& bile duct) also shifts to the left
o When buds shift, pancreatic tissue from buds fuse to form one mass
o Ventral bud = lower part of head & uncinate process of pancreas
o Dorsal bud = upper part of head, body & tail
x Duct system of ventral & dorsal buds anastomose with each other
o Accessory pancreatic duct bt duct of dorsal bud & duodenum
o Main pancreatic duct formed distally by duct of dorsal bud & proximally by ventral bud
Opens into duodenum at the major duodenal papilla with bile duct
x Islets of Langerhans: secretory elements of pancreas; formed by primitive duct system
x Annular Pancreas: pancreatic tissue surrounds duodenum completely & may obstruct it
x Divided pancreas: parts of pancreas derived from dorsal & ventral buds fail to fuse with ea other
x Accessory pancreatic tissue may be found in stomach, duodenum, jejunum, Meckel’s
diverticulum, gall bladder, spleen
x Inversion of pancreatic ducts: embryonic arrangement of ducts persists and greater part of
pancreas is drained through minor duodenal papilla
Spleen
x Collection of mesenchymal cells in dorsal mesogastrium (some from coelomic epithelium)
x Mesenchymal cells Æ Lymphoblasts and other blood-forming cells
o Proliferate = mass which projects left & covered by peritoneum
x Dorsal mesogastrium
o Gastrosplenic Ligament: extends from stomach to spleen
o Lienorenal ligament: extends from spleen to posterior abdominal wall
Fuses to post abd wall, fold of peritoneum passes from spleen to left kidney
x Fusion to post wall + change in orientation of stomach Æ spleen lies on left side
x Forms left boundary of lesser sac of peritoneum
2
x Lobulated spleen
x Spleen may be absent (very rare)
x Accessory spleens can be seen at hilum of spleen, gastrosplenic lig or lienorenal lig, w/in
pancreas, along splenic artery
x Situ inversus Æ spleen onn right side of abdomen; liver on left side
Anomalies of the Extrahepatic duct system

x Abnormal length
o Various ducts join eo Æ some of them may be abnormally long or short
x Abnormal mode of termination
o Cystic duct joins left side of common hepatic Æ passing in front/behind to reach left side
o Cystic duct may end in right hepatic duct
o Cystic duct may pass downwards, anterior to duodenum before joining common hepatic
o Bile duct opens into pyloric or cardiac end of stomach
x Atresia Æ parts of whole duct system missing
x Duplication Æ parts of duct system duplicated
o accessory ducts from right lobe may terminate in right hepatic duct, cystic duct, bile duct
or even directly into gall bladder
The Respiratory System

x From median diverticulum of foregut
x Lining epithelium from endoderm
x CT, cartilage, muscle from splanchnopleuric mesoderm
x Tracheobronchial groove: midline groove (diverticulum) in floor of developing pharynx, caudal
to hypobranchial eminence
o Flanked by 6th pharyngeal arches
o Distal part separated from esoph, but cranial part cont’s comm. w/ pharynx
x Lung buds Æ arise from bifid of free caudal end of diverticulum Æ bronchi & parenchyma
x Cranial to bifurcation of diverticulum Æ larynx & trachea
Larynx
x Develops from cranial most part of respiratory diveritculum
x Inlet of larynx persists as comm. bt diverticulum & pharynx
x Epiglottis: formed by caudal part of hypobranchial eminence
x Thyroid cartilage: from 4th arch
x Cricoid cartilage: from 5th arch
x Arytenoid cartilage: from 6th arch
x Laryngeal muscles derived from branchial mesoderm as indicated by their nerve supply
x Laryngocoele: laryngeal saccule abnormally large; goes beyond larynx proper = swelling in neck
x Congenital stenosis or atreasia: stenosis or atresia of larynx
x Duplication of entire or part of larynx
x Laryngoptosis: larynx lies down in the neck; part of it may be behind the sternum
x One or more laryngeal cartilages may be absent
Trachea & Bronchi

x Trachea Æ part of respiratory diverticulum (lies bt point of bifurcation & larynx)
3
x R & L Principal Bronchi Æ primary divisions of respiratory diverticulum

o Left division: more transversely than right, soon shows 2 divisions Æ 2 lobar bronchi
o Right division: divides into 3 lobar bronchi
x Tracheo-esophageal fistulae: atresia of esophagus often accompanied by abnormal comm. bt
esophagus & trachea Æ connected at some points
x Diveritculum may arise from the trachea
x Accessory bronchi may arise from the trachea; these bronchi may be
o Blind
o Supply a mass of lung tissue (accessory lobe) which is not a normal part of the lungs
o Replace a normal bronchus (ie: apical) in one of the lungs
x Trachea may be absent (very rare) Æ bronchi may arise from a blind bifurcation or from esoph
Lungs
x Substance of the lungs formed by further subdivisions of lobar bronchi
o Before birth Æ 17 subdivisions of each main bronchus
o After birth Æ 23 subdivisions
x Alveoli formed after est of bronchial tree & expansion of terminal parts of tree
x Lung parenchyma devl’p from lobar bronchi
o Separated by mesoderm Æ forms CT basis of lung & gives rise to pleura
o Pleura: lines surface of each lobe Æ separated by fissures
x Before birth Æ subdivisions of bronchial tree lined by cubical epithelium; Canalicular phase
x After birth Æ onset of respiration Æ alveoli become dilated and lining epith becomes thin
x Some cells within respiratory passages become specialized for production of surfactant
o Surfactant Æ reduces surface tension; thin layer lining alveoli
Prevents collapse of alveoli during expiration
o Before birth Æ respiratory passages full of fluid
o After birth Æ start breathing Æ fluid rapidly absorbed & partly expelled; ĹRIDOYHROL
o Premas Æ deficiency of surfactant = difficulty in expansion of lung & could cause death
x Pulmonary circulation est in early fetal life
x Foramen Ovale & ductus arteriosus: most of blood circuited through these structures first
x Amount of blood circulating through lungs progressively increases
o 7th month Æ circulation rich enough to provide adequate oxy for sustaining life
x Agenesis & Hypoplasia: complete lung or one of its lobes (& assoc bronchi) may fail to devl'p
or may remain underdeveloped
x Absence of fissures Æ reduction of # of lobes
x Three-lobed left lung Æ transverse fissure may appear on left side = extra lobe in left lung
x Medial basal segment (cardiac lobe) of left lung may be separated by a fissure from rest of lobe
x Superior segment of lower lobe may be separated in the same way
x Upper lobe of right lung may come to lie medial to azygous vein Æ Axygous Lobe
o Azygous vein is suspended from wall of thorax by a fold of parietal pleura (mesoazygous)
x Accessory lobes: usually connected to bronchi that are not part of the normal bronchial tree
o Upper accessory lobe from trachea, above bifurcation
o Lower accessory lobe from esophagus; occasionally lobe won’t have a bronchus
x Sequestration of lung tissue: area of embryonic lung tiss may separate frm tracheobronchial tree
o Lobar sequestration Æ tissue may form a complete lobe
o Most commonly seen in lower lobe of left lung
x Lung Hernia Æ part of lung may be herniated
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o Through inlet of thorax

o Through a defect in thoracic wall
o Into mediastinum
o Into opposite pleural cavity
x Displaced bronchi may arise from trachea above its bifurcation or from esophagus
o May supply
A normal segment of one of the lungs
An accessory lobe
May be blind
Body Cavities
x Pericardial, Pleural, Peritoneal cavities from intra-embryonic coelom
x Lateral plate mesoderm splits into
o Parietal (somatopleuric)
o Visceral (splanchnopleuric)
x Mesothelium: flattened epithelial lining from differentiation of mesodermal cells lining cavities
o gives the peritoneum, pleura and pericardium their smooth surfaces
x Intraembryonic coelom Æ horseshoe shaped cavity w/ narrow midline part and 2 lateral parts
o Midline parts Æ lie cranially in the embryonic disc Æ Pericardial Cavity
o Two lateral limbs of the coelom Æ Peritoneal Cavity
x For some time pericardial cavity and peritoneal cavity are connected to each other by a pair of
narrow pericardio-peritoneal canals.
x These canals undergo great enlargement to form the pleural cavities
Pleural cavity
x After formation of head fold Æ pericardium comes to lie on the ventral aspect of the embryo
x Pericardio-peritoneal canals wind backwards on either side of the foregut
o Lung buds from foregut invaginate these canals
As the bud enlarges to form lungs, the canals balloon out = pleural cavities
x Pericardio-pleural opening: each pleural cavity comm. with the pericardial cavity
x Pleuro-peritoneal opening: each pleural cavity comm. w/ peritoneal cavity
x Openings are closed by the formation of the pericardio-pleural membranes and the formation of
pleura-peritoneal membranes respectively
Peritoneal Cavity
x Peritoneal cavity formed from the two limbs of the horseshoe shaped intra-embryonic coelom
x Two parts fuse to form one cavity Æ lateral folding of the embryonic disc
x Two parts of the cavity remain separate at the cranial end of the abdomen
x Attachment of mesentry of the primitive gut on posterior abdominal wall is initially at midline
x Changes in rotation of the gut Æ some parts of the gut becoming retroperitoneal
o The line of attachment of the mesentry becomes complicated
x Peritoneal cavity subdivides into many pockets that are partially sep’d by folds of peritoneum
Development of Lesser Sac of Peritoneum

x Three distinct processes involved in the formation of lesser sac of peritoneum
x Dorsal mesogastrium: connects stomach to post wall of the abd (initially – thick membrane)
o Two small cavities appear in this membrane
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o Right and left pneumato-enteric recesses

Left recess Æ disappears
Right recess Æ enlarges and opens into the peritoneal cavity
x cavity of this recess enlarges considerably and extends to the left to form
the part of the lesser sac that lies behind the stomach
x extends cranially, on the right side of the esophagus and behind the liver
x With est of the diaphragm, upper most part of this cranial extension comes
to lie above the diaphragm Æ infracardiac bursa
o Right penuomato-enteric recess extends to the left Æ stomach changes orientation Æ
posterior border now faces left Æ greater curvature
Ventral border now faces the right and forms the lesser curvature
Ventral mesogastrium Æ lesser omentum
Stomach orientation changes Æ part of peritoneal cavity lies behind the lesser
omentum Æ part of the lesser sac
x Altered orientation of stomach Æ dorsal mesogastrium att to greater curvature subdivided (2)
o Part A Æ left margin of lesser sac
passes from stomach to spleen as gastro-splenic ligament
passes from spleen to left kidney as lienorenal ligament
o Part B Æ passes from lower border of stomach to post abd wall Æ greater omentum
Increasingly projects below level of stomach & becomes folded on itself
Space within fold Æ lower part of lesser sac
Diaphragm
x Partition separating thoracic and abdominal cavities
x Cranial Æ Pericardial and pleural cavities
x Caudal Æ Peritoneal cavity
x Cranial part of liver helps form the diaphragm
x Septum transversum forms a mesodermal mass lying caudal to the pericardial cavity
o separates the pericardial and peritoneal cavities
o Posterior Æ pleural and peritoneal cavities comm thru the pleuro-peritoneal canals that
lie o either side of esophagus
x partition b/w the thorax and abdomen is completed when the pleuro-peritoneal canals are closed
by the formation of the pleura-peritoneal membranes
x Development of Diaphragm
o pleural cavities increase size Æ thorax as a whole also expands
o diaphragm also enlarges at the expense of body wall
o diaphragm formed from the following components
septum transversum
pleuro-peritoneal membranes
ventral and dorsal mesenteries of esophagus
mesoderm of body wall ĺLQFOXGLQJPHVRGHUPDURXQGWKHGRUVDODRUWD
o nerve supply of the diaphragm from the C3, C4, C5 nerves
o diaphragm has undergone great migration in caudal direction during development
x Diaphragmatic hernias: Abdominal contents may pass through gap in muscle where parts of
diaphragm failed to develop
o Posterolateral Æ due to failure of a pleuro-peritoneal canal to close
o Posterior Æ due to failure of the development of the crura
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o Retrosternal Æ abnormally large gap between the sterna and costal parts of the muscle
o Central Æ thru dome of diaphragm (sometimes entire half of diaphragm absent)
x Accessory diaphragm in the thoracic cavity Æ divides the lung into two parts
x Congenital eventration of the diaphragm Æ muscle may be thin and aponeurotic Æ may bulge
upwards into the thorax (unilateral or confined to a small area)
Timetable of Events

3 weeks The hepatic bud appears
The pancreatic bud also appears soon after
4 weeks Septum transversum is established
Tracheobronchial diverticulum is formed
6 weeks The diaphragm descends to the thoracic level
7 weeks Fusion of dorsal & ventral pancreas
3 months Bile formation begins
Pancreatic islets are formed
5 months Insulin secretion begins
7

Cardiovascular System
x Septum Primum & Secondum: separates primitive atrium into R & L atria
x Foramen ovale: bt 2 septa, valvular = passage of blood from right Æ left atrium
x Ventricles formed by proximal 1/3 of bulbus cordis, cornus & primitive ventricle; R & L sep by:
o Interventricular septum: grows from floor of primitive ventricle upwards
o Bulbar septum: divides conus into 2 parts
o gap bt 2 parts of conus filled via prolif of A-V cushions (formed by A-V canal)
x Truncus arteriosus continuous with aortic sac Æ has R & L horns
o Each horn continuous with 6 pharyngeal (aortic) arch arteries – join dorsal aorta; only
3rd, 4th, 6th arch remain; caudal part of R & L dorasal aortae fuse = 1 median aorta
x Arch of aorta Æ left horn & left 4th arch artery of aortic sac
x Descending aorta Æ left dorsal aorta & partly from fused median vessel
x Brachiocephalic artery Æ right horn of aortic sac
x Common Carotid Artery Æ part of 3rd arch artery
x Pulmonary Artery Æ 6th arch artery
x Arteries to the gut Æ ventral splanchnic branches of dorsal aorta
x Renal, suprarenal & gonadal arteries Æ lateral splanchnic branches of dorsal aorta
x Arteries to body wall & limbs Æ dorsolateral (somatic intersegmental) branches of aorta
x L Subclavian Æ 7th cervical intersegmental artery
x R Subclavian Æ 7th cervical intersegmental artery & R 4th arch artery
x Portal v/.ein Æ anastomosis between R & L vitelline veins
x Superior Vena Cava Æ part of R ant cardinal vein & R common cardinal vein
x IVC Æ R post cardinal, R subcardinal, R supracardinal veins & R hepatocardiac channel
The Heart
x From splanchnopleuric meso cranial to prochordal plate Æ cardiogenic area
x Right and left endothelial heart tubes fuse Æ median tube with dilatations
o Bulbus cordis
dilated proximal 1/3 Æ primitive R ventricle (trabeculated part)
middle 1/3 = conus Æ outflow tracts of R & L ventricles
distal 1/3 = truncus arteriosus Æ ascending aorta & pulmonary trunk
x continuous with aortic sac which is cont’s with R & L arch arteries
x arteries arch backwards & become cont’s with R & L dorsal aortae
o Ventricle Æ primitive L ventricle (trabeculated part)
o Atrium Æ partitioned into R & L atria
o Sinus Venosus Æ right & left horns; venous end of heart
1 vitelline vein (from yolk sac) Æ part of inferior vena cava
1 umbilical vein (from placenta) Æ disappears
1 common cardinal vein (from body wall) Æ part of superior vena cava
left horn retrogresses; remnant forms part of coronary sinus
o Bulbo-ventricular sulcus Æ between ventricle & bulbus cordis
o Atrio-ventricular canal Æ connects atrium & ventricle
1
Formation of Atria
1. Opening between sinus venosus & primitive atrial chamber becomes narrower and shifts right
2. R & L venous valves fuse cranially Æ septum spurium
3. A-V canal divides into R & L halves
4. atrio-ventricular cushions form on dorsal & ventral walls then fuse Æ septum intermedium
Formation of Interatrial Septum

1. septum primum from roof of atrium and left of septum spurium grows downawards towards a-v
canal & fuses with septum intermedium
a. foramen primum: gap between primum & intermedium Æ blood flows from RA to LA
b. foramen secundum: forms from break down of upper part of septum primum before
forament primum is closed = another path for blood flow after closure
2. septum secundum grows down from room of atrium to right of septum primum; overlaps free
upper edge of primum Æ blood has to flow R-to-L thru interval bt septa (foramen ovale)
a. After birth Æ LA receives oxy blood from lungs, foramen ovale no longer necessary;
obliterated via fusion of septum primum & secundum
b. Annulus ovalis = lower free edge of septum secundum
c. Fossa ovalis = septum primum
Development of the Right Atrium

x Mainly derived from right half of primitive atrium
x Enlargement of sinuatrial orifice = sinus venosus & right part of a-v canal absorbed into RA
x Sinus Venosus
o Left horn stays small and eventually becomes part of coronary sinus
o R Common Cardinal Vein becomes part of SVC
o R Vitelline vein forms terminal part of IVC
o Venae cavae & coronary sinus open into RA after absorption into it
x Right margin of sinuatrial orifice (R venous valve) expands and divides into 3 parts
o Crista terminalis Æ at junc’n of part of RA derived from sinus venosus & atrium proper
o Valve of inferior vena cava
o Valve of coronary sinus
Development of Left Atrium

x Left half of primitive atrium & A-V canal and proximal parts of pulmonary veins
x Absorption of Pulmonary Veins
o When septum primum is to forming, single pulmonary vein opens into left half of atrium
o Gradually, proximal parts of pul veins absorbed into atrium = 4 separate veins
Development of Ventricles
Bulbus Cordis
x Spiral septum: divides truncus arteriosus into ascending aorta & pulmonary trunk,
o formed by union of superior (R) & inferior (L) truncus cushions
o at lower end, PT is ventral to aorta, but upper end Æ PT is found left of aorta
x Conus Æ outflow tracts of both R & L ventricles
x Proximal 1/3 merges with cavity of primitive ventricle
x Bulbo-ventricular Cavity
o Dilated lower part (from proximal 1/3 & primitive ventricle) comm. with atria
o Conical upper part (from conus) comm. w/ truncus arteriosus
2
Formation of Interventricular Septum

x Cavity formed after conus & proximal 1/3 have merged into prim ventricle is subdiv into R & L
o Each half comm. w/ corresponding atrium
o RV opens into PT and LV into Aorta
x Interventricular septum grows upwards from floor of bulbo-ventricular cavity and divides the
lower part of cavity into R & L then partially fuses with septum intermedium
x R & L bulbar ridges from wall of bulbo-ventricular cavity grow towards eo Æ bulbar septum
x Bulbar septum grows downwards towards interventricular septum but not all the way = gap
o Prolif of atrio-ventricular cushions in gap
Further Development of the Heart

x After head fold Æ splanchno meso & heart are dorsal to pericardial cavity & ventral to foregut
o Tube invaginates pericardial sac from dorsal side of cavity Æ splanchno meso on dorsal
side forms myoepicardial mantle Æ completely surrounds heart tube
o Myoepicardial mantle Æ myocardium & epicardium
o Parietal Pericardium from somatopleuric mesoderm
x Exterior part of Heart
o Dorsal mesocardium: suspends heart tube from dorsal wall of pericardial cavity
o Caudal part of heart tube (atrium & sinus venosus) embedded w/in septum transversum
o Bulbus cordis & ventricle lie w/in pericardial cavity
Bulbo-ventricular loop: formed when this part of tube is folded over itself
o Folding = atrium & sinus venosus freed from septum transversum Æ now lies behind and
above ventricle Æ heart tube S-shaped
o Bulbo-ventricular sulcus separates bulbus cordis & ventricle
Becomes shallower Æ conus + ventricle = 1 chamber Æ comm. w/ truncus art
o Atrial chamber is behind upper part of ventricle & truncus arteriosus
Expands Æ projects forwards on either side of truncus = definitive shape of heart
x Sinus Venosus
o Becomes separated from atria by grooves on lateral wall of heart tube at junc’n
o Right groove remains shallow, but left one becomes very deep Æ separated frm atrium
o Blood enters thru right half of sinus & left horn becomes tributaries of right half
Sinuatrial orifice now on right side of posterior aspect of atrial chamber &
becomes vertical; margins Æ R & L venous valves
x Interatrial Septum
o Crista dividens: lower edge of septum secundum, thick and firm
o Upper edge of septum primum think & mobile (flap-like) Æ allows blood to flow R Æ L
o After birth Æ LA receives blood from lungs = Ĺ3!5$ closure of foramen ovale
x Interventricular Septum
o Downward enlargement of R & L ventricular cavities on either side of septum
o Membranous part: anterior & posterior
Anterior Æ separates R & L ventricles; derived from prolif of tissue from
endocardial cushions
Posterior Æ separates L ventricle from RA (aka atrioventricular septum); since
interatrial & interventricular septa don’t meet atrioventricular cushions at same
line Æ separates LV from RA
x Heart Valves
o Mitral & Tricuspid formed by prolif of CT under endocardium of L & R a-v canals
o Pulmonary & Aortic from endocaardial cushions at junc’n of t arteriosus & conus
3
o 2 cushions on R & L in wall of conus grow & fuse with eo

Separation of aortic & pulmonary = subdivision of cushions (part to ea orifice)
o Anterior & posterior cushions also appear at the same time
o 3 cushions of each aortic & pulmonary valves Æ 3 cusps
o Pul valve rotates from ventral side of aortic valve to ventral & left of valve
o After rotation Æ definitve positions
x Conducting System
o Pacemaker first lies in caudal part of left tube
o After fusion of tubes Æ pacemaker in sinus venosus Æ near opening of SVC
o AV node & AV bundle = left wall of sinus venosus & in AV canal
o After sinus venosus absorbed into RA Æ AV node lies near interatrial septum
Pericardial Cavity
x Part of i-e coelom in midline, cranial to prochordal plate
x After head fold Æ lies on ventral side of body of embryo
x Heart tube invaginates pericardial sac from dorsal aspect
x Parietal layer of serous & fibrous pericardium from somatopleuric meso on ventral side
x Visceral serous pericardium from splanchnopleuric meso on dorsal side of pericardial cavity
x Heart tube initially suspended w/in pericardial cavity by dorsal mesocardium
o After dorsal meso disappears Æ layers of pericardium cont’s at arterial & venous ends
x Folding Æ Arterial & venous ends get closer; space in bt = transverse sinus of pericardium
x Arterial end Æ aorta & pulmonary trunk
x Venous end Æ SVC, IVC & 4 pulmonary veins
x Rearrangement of veins at venous end = formation of isolated pouch of pericardium near
pulmonary veins Æ oblique sinus of pericardium
Anomalies of Position
x Dextrocardia: all structures that are usually on right are on left and v.v.
x Ectopia cordis: heart is exposed on front of chest due to defective devl’t of chest wall
Atresia or Stenosis
x Atresia: orifices have no opening at all
x Stenosis: any of the orifices may have too narrow opening
o Aortic & Pulmonary passages show supra- or subvalvular stenosis
o Pulmonary Æ foramen ovale & ductus arteriosus is patent Æ blood flows into aorta
x Openings may be too large Æ valves become incompetent
Abnormal Growth
x Accessory cusps in valves
x Congenital tumors
x LA may be partially subdivided by a transverse septum
x Hypoplasia Æ myocardium poorly developed
Defective Formation of Septa Æ abnormal passages

x Interatrial
o Osteum primum defect: septum primum fails to reach AV endocardial cushions; foramen
primum persists; also caused by defective formation of endocardial cushions
4
o Osteum secundum defect: septum secundum fails to devl’p Æ foramen secundum

remains wide open
o Patent foramen ovale: septum primum & secundum normal, but oblique valvular
passage in between remains patent (only problematic if there is shunt of blood thru it)
o Premature closure of foramen ovale (before birth): hypertrophy of RA & RV & left side
is underdeveloped
x Interventricular Æ most common; in membranous or muscular part of septum
x Patent truncus arteriosus: spiral septum not formed at all; partial absence of septum = shunts bt
aorta and pulmonary trunk
x AV canal defect or persistent AV Canal: defective formation of AV cushions Æ all 4 chambers
inter-communicate; interatrial & interventricular septa incomplete
Tricuspid atresia: fusion of endo cushions too much to the right; upper part of IV septum defective
x Ĺ3LQ5$Æ foramen ovale doesn’t close
x Cor biloculare: 2 chambered heart Æ common ventricle & atrium
x Cor triloculare: 3-chambered heart; single ventricle with 2 atria,
x Cor triloculare biventriculare: 3-chambered with single atrium & 2 ventricles
Fallot’s Tetrology
x Interventricular septal defect
x Aorta overriding free upper edge of ventricular septum
x Pulmonary stenosis
x Hypertrophy of Right Ventricle
Anomalies of Relationship of Chambers to Great Vessels

x Transposition of GVs: aorta from RV & PT from LV
x Taussing-Bing Syndrome: aorta from RV & PT overrides both RV & LV Æ IV septal defect
x SVC & IVC end in LA
x Pulmonary veins end it RA or in one of its tributaries
The Arteries
Pharyngeal Arch Arteries
x R & L primitive aortae cont’s with 2 endocardial heart tubes
o Ventral aorta Æ ventral to foregut
o Arched portion Æ 1st pharyngeal arch
o Dorsal Aorta Æ dorsal to gut
x After fusion of tubes Æ R & L ventral aortae fuse partially = aortic sac, R & L horns of sac
x Successive arterial arches in 2nd-6th pharyngeal arches Æ connected ventral to R or L horns of
aortic sac and dorsally to dorsal aorta
x Most of 1st & 2nd arch disappear
o 1st Æ maxillary artery (in adult)
o 2nd Æ stapedial artery (in fetus); may contribute to external carotid artery
x 5th also disappears
x Aortic sac Æ 3rd, 4th, & 6th arches
o 3rd & 4th Æ open into ventral part
o 6th Æ open into dorsal part
x Spiral septum extends into aortic sac & fuses with posterior wall
5
o blood from pulmonary trunk Æ 6th arch artery

o blood from ascending aorta Æ 3rd & 4th arch arteries
x Dorsal aortae grow cranially beyond 1st arch
o ductus caroticus: portion of dorsal orta bt 3rd & 4th arteries disappears
o right dorsal aorta bt 4th arch & point of fusion of dorsal aortae disappears
o lateral intersegmental branches Æ body wall
7th cervical intersegmental A supplies upper limb bud; att to dorsal aorta near att
of 4th arch artery
x Lung bud branch given off by each 6th arch artery
o Right Æ part of 6th bt lung bud & dorsal aorta disappears
o Left Æ same part becomes ductus arteriosus Æ carries most blood from RV to dorsal
orta; obliterated after birth Æ ligamentum arteriosum
x External Carotid Artery develops from cranial buds given off by each 3rd arch artery
x Ascending Aorta & Pulmonary Trunk Æ from truncus arteriosus
x Arch of aorta Æ ventral part of aortic sac, left horn of sac & left 4th arch artery
x Descending aorta Æ left dorsal aorta below att of 4th arch, & fused median vessel
x Brachiocephalic Artery Æ right horn of aortic sac
o Proximal part of R Subclavin Æ right 4th arch artery, 7th cervical intersegmental
o Common Carotid A Æ part of 3rd arch, proximal to external carotid bud
x L Subclavian Æ entirely from 7th cervical intersegmental artery
x Internal Carotid Artery Æ formed by distal portion of 3rd arch with dorsal aorta
x External Carotid Artery Æ from bud of 3rd arch artery
x Pulmonary Arteries from 6th arch bt PT and branches to lung buds
x Double aortic arch Æ arterial ring can compress trachea & esophagus
x Right aortic arch Æ aortic arch disappears on left side instead of right
x Patent ductus arteriosus Æ ductus arteriosus isn’t occluded after birth
x Right Subclavian arises as last branch of aortic arch instead of from brachiocephalic
o with aorta = arterial ring enclosing trachea & esophagus Æ compress & obstruct tubes
o right recurrent laryngeal doesn’t hook around subclavian, passes directly to larynx
o arterial ring can also be formed if dorsal aorta persists on both sides
x Ductus Caroticus may persist Æ left internal carotid arises directly from aortic arch & right
internal carotid from subclavian
x Interrupted Aortic Arch: segment of aortic arch missing Æ ascending aorta ends by supplying
LCCA; left subclavian from distal segment, receives blood thru patent ductus arteriosus
x Coarctation of the Aorta: localized narrowing of aorta Æ partial or complete obstruction of
blood flow; most frequently seen near att of ductus arteriosus to aorta
o Postductal: distal to attachment of ductus arteriosus; many anastomoses est bt branches
of aorta above and below level of constriction
o Preductal: proximal to att; R ventricle supplies distal part of body via ductus arteriosus
Other Arteries
x 3 groups of branches from primitive dorsal aortae
o Ventral splanchnic arteries Æ supply gut only celiac, superior & inf mesenteric remain
to supply infradiaphragmatic part of foregut, midgut & hindgut; bronchial & esophageal
arteries are also remnants of vessels
o Lateral/intermediate splanchnic Æ renal, suprarenal, phrenic, spermatic & ovarian
6
o Dorsolateral (somatic intersegmental) Æ run bt 2 adjacent segments; retain original

intersegmental arrangement in thoracic & lumbar regions Æ intercostal & lumbar As
Ventral gives off lateral branch Æ limb buds
x Anastomoses are formed on ventral aspect of body wall near midline
x Internal thoracic, superior & inferior epigastric
Dorsal supplies muscles of back; spinal branch runs medially Æ spinal cord
Longitudinal anastomoses
Neck Æ dorsal branches connected by anastomoses
x Pre-costal: in front of necks of ribs
o Thyrocervical trunk, ascending cervical A, superior ICA
x Post-costal: bt costal elements & transverse processes Æ Vertebral Artery
x Post-transverse: behind transverse processes Æ Deep Cervical A
x th
7 Cervical Intersegmental Artery
o Main stem from subclavian; divides into dorsal, ventral & lateral divisions
o Dorsal Æ stem of vertebral artery
o Larteral Æ upper limb (axillary & brachial arteries)
o Ventral Æ stem of internal thoracic (mammary) artery
Vertebral Artery
x 1st part of artery from origin to point of entry into foramen transversarum of 6th cervical vertebra,
formed by dorsal division of 7th cervical intersegmental artery
x 2nd part Æ foramina transversaria, from post-costal anastomoses bt 1st & 6th cervical interseg As
Development of Internal Thoracic Artery

x Main stem of artery formed by ventral division of 7th cervical intersegmental artery
x Vertical part (incl superior epigastric) derived from ventral anastomoses bt ventral divisions of
thoracic intersegmental arteries (ICAs)
Arteries of Limbs
x Lateral branches of somatic intersegmental arteries
x Each limb has own axis artery Æ runs along central axis of limb; original axis artery disappears
x Axis artery of upper limb formed by 7th cervical intersegmental artery
o Axillary, brachial, anterior interosseous arteries Æ deep palmar arch
o Radial & ulnar later
x Left subclavian = main stem of 7th cervical intersegmental A & proximal part of lateral division
x Axis artery of lower limb derived from 5th lumbar intersegmental artery Æ branch of internal
iliac and runs on dorsal aspect of thigh; proximally gets linked above with external iliac &
below with popliteal artery
o Inferior gluteal A
o Small artery with Sciatic Nerve
o Part of popliteal artery that lies above level of popliteus muscle
o Distal part of peroneal artery
o Part of plantar arch
Umbilical Artery
x Continuations of distal ends of dorsal aortae
x After fusion of aortae Æ lateral branches of single dorsal aorta
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x Each umbilical artery linked up with that part of 5th lumbar interseg artery Æ internal iliac artery
x After birth Æ proximal part of umbilical artery becomes superior vesical artery; distal part
obliterated Æ medial umbilical ligament
Veins
Visceral Veins
x Vitelline veins: from yolk sac (aka omphalomesenteric veins)
x Umbilical veins: right & left from placenta
x Open into sinus venosus
x Liver Æ in septum transversum
o Vitelline & umbilical veins get broken up into many small channels Æ sinusoids
o Hepatocardiac channels Æ drain into sinus venosus (left disappears)
o Common hepatic vein Æ forms cranial-most part of IVC
o Right umbilical vein disappears Æ all blood reaches developing liver thru left vein
o Ductus Venosus Some sinusoids enlarge to create direct passage connecting left
umbilical vein to right hepatocardiac channel
Portal Vein
x Proximal parts of 2 vitelline veins lie on right & left sides of developing duodenum
x Veinsinterconnected by 3 transverse anastomoses Æ 2 are ventral to duod, 3rd connects dorsally
x Superior mesenteric & splenic veins develop independently & join left vitelline vein
x Parts of vitelline vein disappear:
o Part of Right vitelline vein, caudal to dorsal anastomosis
o Part of Left vitelline vein caudal to entry of superior mesenteric & splenic veins
o Caudal ventral anastomosis
o Left vitelline vein bt dorsal anastomosis & cranial ventral anastomosis
x Portal vein derived from parts of vitelline veins that remain:
o Left vitelline vein bt entry of superior mesenteric & spenic veins & dorsal anastomosis
o Dorsal anastomosis itself
o Right vitelline vein bt dorsal anastomosis & cranial ventral anastomosis
x left branch of portal vein formed by cranial ventral anastomosis & part of left vitelline vein
cranial to the anastomosis
x right branch formed by right vitelline vein cranial to ventral anastomosis
x venae advehentes: sinusoids that carry blood of R & L branches to liver substance
x venae revehentes: sinusoids that drain blood to IVC Æ tributaries of hepatic veins
x left umbilical vein ends in left branch of portal vein, ductus venosus connects left branch of
portal vein to IVC (right hepatocardiac channel)
Somatic Veins
x Anterior cardinal Æ drain cranial part of embryo (incl. brain)
o Joined by subclavian veins Æ drain forelimbs; interconnected via transverse anastomosis
o Left ant cardinal caudal to anastomosis retrogresses & left common cardinal retrogress
x Posterior cardinal Æ drain caudal part of embryo
x Common cardinal (aka Duct of Cuvier) open into corresponding horns of sinus venosus
x Superior Vena Cava Æ opens into RA (right horn of sinus venosus)
o Right anterior cardinal vein caudal to transverse anastomosis w/ left ant cardinal
o Right common cardinal
8
x R Brachiocephalic Vein from anterior cardinal bt point of junc’n w/ subclavian & point of
junc’n with transverse anastomosis
x L Brachiocephalic Vein derived from
o L ant cardinal vein corresponding to R BCV
o Transverse intercardinal anastomosis
x Internal Jugular veins from parts of ant cardinal veins cranial to junction w/ subclavian
x External Jugular veins secondary channels Æ not derived from anterior cardinal veins
x Intersegmental veins from body wall Æ anterior & posterior cardinal veins
x Subclavian veins formed by enlargement of one of these veins in region of upper limb bud
x Left Superior Intercostal Vein & Coronary sinus from retrogressing left veins
o Left superior intercostal vein Æ left ant cardinal vein caudal to transverse anastomosis &
most cranial part of left pos cardinal vein; 2nd & 3rd intercostal veins drain into this vein
o Coronary sinus Æ medial part from left horn of sinus venosus; lateral part from proximal
part of LCCV
x Oblique vein of left atrium Æ remaining part of LCCV
Veins of Abdomen
x Posterior cardinal veins: cranial ends join anterior cardinal veins Æ common cardinal veins
o Near caudal ends, receive veins of lower limb bud & pelvis
o Caudal ends interconnected via transverse anastomosis
x Subcardinal Veins: formed in relation to mesonephros
o Cranially & caudally comm. w/ posterior cardinal veins
o Receive veins from developing kidneys
o Intersubcardinal anastomosis: 2 subcardinal interconnected at level of renal veins
o Cranial part also est anastomosis w/ right hepatocardiac channel
x Supracardinal veins (aka thoracolumbar veins): comm. cranially & caudally w/ posterior
cardinal veins; also comm. with subcardinal veins thru anastomoses which join subcardinals just
below renal veins
x Inferior vena cava derived from (caudal to cranial):
o Lowest part of R posterior cardinal vein (bt junc’n w/ supracardinal and anastomosis
bt 2 posterior cardinals
o Lower part of R supracardinal vein (bt junc’n with posterior cardinal & supracardinal-
subcardinal anastomosis)
o Right supracardinal-subcardinal anastomosis
o Renal segment of IVC Æ Right subcardinal vein bt above anastomosis & the anast bt
subcardial vein & R hepatocardiac channel
o Hepatic segment of IVC Æ right hepatocardiac channel
x Right common iliac vein from most caudal part of right posterior cardinal vein
x Left common iliac vein = anastomosis bt 2 posterior cardinal veins
x Right renal vein Æ mesonephric vein that originally drains into subcardinal vein Æ opens into
part of vena cave that is derived from subcardinal vein
x Left renal vein
o Mesonephric vein that originally drains into left subcardinal vein
o Small part of left subcaridnal vein
o Inter-subcardinal anastomosis (lies in front of aorta)
x Suprarenal Veins = remnants of part of subcardinal veins above intersubcardinal anastomosis
x Testicular/Ovarian veins = remnants of parts of subcardinal veins below intersubcardinal anast
9
Azygos System of Veins

x Drainage from posterior cardinal vein (body wall) transferred to azygos chain
x Cranially, these channels drain into posterior cardinal veins
x Channels from both sides comm. w/ eo via vessels that run to aorta
x L azygos loses comm. w/ post cardinal & blood drain into right azygos line thru post-aortic anast
x Azygos vein formed from
o Vein of right azygos line
o Most cranial part of right posterior cardinal vein thru which it opens into SVC
x Vertical parts of hemiazygos & accessory hemiazygos reps left azygos line; horizontal parts
formed by post-aortic anastomoses bt azygos lines of both sides
x 2nd & 3rd left intercostal veins retain connection with left posterior cardinal vein Æ drained thru
left superior intercostal vein
x Abdominal parts of veins of azygos line rep by ascending lumbar veins
Anomalies of Veins
x Left superior vena cava: failure of left anterior & common cardinal veins to retrogress; opens
into RA thru large coronary sinus; normal SVC might be smaller or even absent
x Double IVC: generally, only below level of renal veins
o Persistence of both subcardinal & supracardinal veins below level of kidneys Æ Both
channels present on right side
o Additional channel may form on left side
x Left IVC: infrarenal part of vena cava my be present on left side only
x Azygos continuation of IVC: hepatic segment of IVC may be absent due to devlp’t of anast bt R
subcardinal vein & R hepatocardiac channel Æ upper part of IVC follows course of azygos
vein & opens into SVC; hepatic veins open into RA at usual site of IVC
x Pre-ureteric vena cavae: IVC may be anterior to right ureter; ureter hooks around to left side of
vena cava; normally caused when infrarenal part of vena cava devl’ps from subcardinal vein
instead of supracardinal vein (posterior to ureter)
Fetal Circulation
x Source of oxy blood is placenta not lung
x Oxy blood from placenta Æ umbilical vein Æ left branch of portal vein Æ IVC via ductus
venosus (sphincter-like controls blood flow)
x Oxy-rich blood reaching RA via IVC towards foramen ovale Æ div into 2 by septum secundum
o Most passes thru foramen ovale Æ LA
o Rest gets mixed up with blood returning to RA thru SVC & passes into RV
x From right ventricle, mostly deoxy blood, enters PT Æ only some reaches lungs & passes into
LA; most is short-circuited b yductus arteriosus into aorta
x LA receives oxy blood from RA & some deoxy blood from lungs
o Oxy rich blood passes into LV and then into aorta
o Some passes into carotid & subclavian As to supply brain, head & neck & upper limb
o Rest gets mixed up with poorly oxygenated blood from ductus arteriosus Æ parts of body
that are supplied by branches of aorta arising distal to its junc’n with ductus arteriosus,
receive blood with only moderate oxygen content
o Much of the blood of aorta carried by umbilical arteries to placenta where it is
oxygenated & returned to the heart
10
Changes to Circulation at Birth

x Muscle in wall of umbilical As contracts & occludes lumen Æ no loss of fetal blood to placenta
x Lumen of umbilical veins & ductus venosus also occlude few minutes after birth Æ all fetal
blood in placenta has time to drain back to fetus
x Ductus arteriosus occluded Æ all blood from RV now goes to lungs to be oxygenated
o Initial closure caused by contraction of muscle in vessel wall
o Later, intima proliferation obliterates the lumen
x Pulmonary vessels increase in size Æ much larger volume of blood reaches left atrium from
lungs Æ Ĺ3LQ/$ 3LQ5$GLPLQLVKHGEFEORRGIURPSODFHQWDQRORQJHUUHDFKHVLW
o Since P in LA > RA = closure of valve of foramen ovale
x Vessels that are occluded are replaced by fibrous tissue = ligaments
o Umbilical Arteries Æ medial umbilical ligaments
o Left Umbilical Vein Æ ligamentum teres of liver
o Ductus venosus Æ ligamentum venosum
o Ductus arteriosus Æ ligamentum arteriosum
Lymphatic System
x Lymph sacs Æ independent formations from mesenchym
x R & L Jugular Sacs: near junc’n of post cardinal & subclavian veins
x R & L Posterior (Iliac) Sacs: lie around corresponding common iliac vein
x Retroperitoneal sac: unpaired; lies in relation to root of mesentery
x Cisterna chyli: unpaired; lies in midline caudal to retroperitoneal sac
x Lymphatic vessels = extension from sacs or may form de novo & extend into various tissues
x All sacs except cisterna chyli are invaded by CT & lymphocytes Æ lymph nodes
x Thoracic Duct: derived from R & L channels that connect cisterna chyli to corresponding
jugular sac; 2 channels anastomose across midline
o From caudal part of R channel, anastomosis bt R & L channel, & cranial part of L chanl
x Right Lymphatic duct from cranial part of right channel
Time Table of Events

3rd week Blood & vessel forming cells (angioblastic islands) appear
Cardiogenic area, heart tubes & pericardium have formed
4th week Heart & pericardium lie ventral to foregut

Subdivisions of heart tube are visible
Heart begins to beat (becomes functional)
Formation of septa in heart begins
Aortic arches start appearing in cranial to caudal sequence (most of 1st arch disappears at end of 4th
week)
Veins start forming
5th week spiral septum formed

formation of aortic arches complete
lymphatic sacs form
cardinal, umbilical & vitelline veins formed
conduction system of heart forms
6th week coronary circulation is established

atrio-ventricular valves & papillary muscles forming
7th week heart septa are completely formed
*heart is most susceptible to teratogens between 3-6 weeks and can be affected upto 8th week.
11

Urogenital System
x UG Sys from intermediate mesoderm & primitive UG sinus (UGS) - part of cloaca
x Primitive UGS Æ vesicourethral canal & definitive UGS
o Vesicourethral canal Æ urinary bladder & primitive urethra
o Definitive UGS Æ pelvic part & phallic part
x Kidneys
o Metanephros Æ excretory tubules (nephrons) = lowest part of nephrogenic cord which is
derived from intermediate mesoderm
o Ureteric bud Æ collecting tubules (arises from mesonephric duct) & ureters
x Urinary bladder from cranial part (endoderm)
o epithelium of trigone derived from absorbed mesonephric ducts
x ƂXUHWKUD Æ primitive urethra & pelvic part of UGS
x ƃÆ prostatic urethra (like Ƃ
membranous urethra (from pelvic part of UGS)
penile urethra (from phallic part of UGS)
Terminal part is ectodermal
x Prostate formed by buds from caudal part of vesico-urethral canal & pelvic part of UGS
x Ƃparamesonephric ducts (mesoderm)
o Uterine tubes
o Uterus from utero-vaginal canal (fused R & L parameso ducts)
x External genitalia Æ swellings around UG membrane
x Gonads (testis & ovary) Æ coelomic epithelium covering nephrogenic cord
o PGCs from yolk sac Æ ova & spermatozoa
o Testis formed in lumbar region and later descends to scrotum (ova stay in abdomen)
x Duct system of testis from mesonephric tubules from mesonephric duct
Intermediate Mesoderm
x Intra-embryonic mesoderm
o Paraxial mesoderm Æ somites
o Lateral plate mesoderm Æ intra-embryonic coelom
o Intermediate mesoderm between paraxial & lateral plate meso
x Nephrogenic cord: bulging on posterior abdominal wall, lateral to att of dorsal mesentery of gut
o Forms after folding of embryonic disc & formation of peritoneal cavity
o Surface covered by coelomic epithelium (same as lining of peritoneal cavity)
o Extends from cervical Æ sacral regions of embryo
o Various structures formed on each side of nephrogenic cord thru/o devl’t
Excretory tubules assoc w/ devl’t of kidney
Nephric duct: formed in relation to developing exc tubules Æ mesonephric duct
Paramesonephric duct Æ lateral to nephric duct
Gonad (testis/ovary) from coelomic epith lining medial side of cord
Cloaca
x Subdivides into primitive UGS & rectum
x Primitive UGS subdivides
o Cranial Æ vesico-urethral canal
1
o Caudal Æ definitive UGS

Cranial Æ pelvic part
Caudal Æ phallic part
x Openings of mesonephric ducts at junc’ns of subdivisions of primitive UGS
x UG sys from various structures that devl’p in intermed meso & various subdivisions of cloaca
Development of Kidneys
x Pronephros Æ early kidney; formed in cervical region of nephrogenic cord; non-functional in
humans, disappears right away; but nephric duct ending in cloaca persists
x Mesonephros Æ appears in the thoracolumbar region; series of excretory tubules that drain into
nephric duct (= mesonephric duct); most tubules disappear, but some modified Æ testis duct sys
x Metanephros Æ form of definitive human kidney; found in sacral region; lowest part of cord
o Nephrons Æ excretory tubules
o Metanephric blastema
x Ureteric bud Æ collecting part of kidney; arises from lowest part of nephrogenic cord
o As grows cranially twrds metanephric blastema, growing end dilates Æ ampulla
o Ampulla divides repeatedly
Pelvis of kidney from fusion of first 3-5 generations of branches
Major calyces = next divisions
Minor calyces & collecting tubules from further divisions
o Collecting tubules Æ 1-3 million
o Cells of metanephric blastema that touch ampulla Æ differentiate Æ nephron
Differentiation induced by ampulla
Loosely arranged cells of blastema form solid clumps near ampulla Æ vesicles
Vesicles become pear-shaped & open into ampulla & becomes an S-shaped tube
x Distal end invaginated by tuft of capillaries Æ glomerulus
x Ascent of Kidney (RELATIVE ASCENSION)
o Differential growth of abdominal wall causes kidney to ascend to lumbar region
o Metanephros initially receves blood supply from lateral sacral arteries, but as kidney
becomes higher it is supplied by higher branches of the aorta
o Definitive renal artery = branch of lateral splanchnic branch of aorta at L2
o During ascent, kidneys pass thru fork-like interval bt R & L umbilical arteries (if these
come in the way = block ascent of kidneys)
x Rotation of Kidney
o Hilum initially faces anteriorly Æ gradually rotates so hilum faces medially
x Agenesis: one or both kidneys may be absent
x Hypoplasia: kidney underdeveloped
x Hyperplasia: kidney overdeveloped
x Adrenal tissue may be present within substance of kidney
x Hydronephrosis Æ distension of pelvis with urine due to obstruction in urinary passages
x Duplication Æ extra kidney on one side; may separate or be fused to normal kidney
x Anomalies of Shape
o Horseshoe kidney: lower poles of 2 kidneys fused
Connecting isthmus may be in front of or behind aorta & IVC
Can’t ascend past inferior mesenteric A
o Pancake kidney: 2 kidneys may form one mass, lying in midline or on one side
o Two kidneys may lie on one side, one above the other Æ adjacent poles fused
2
o Lobulated kidney: fetal kidney is normally lobulated; lobulation may persist

x Anomalies of Position
o Kidneys fail to ascend Æ remain in sacral region
o Ascent of kidneys incomplete Æ lumbar region
o May ascend too far Æ can be found in thoracic cavity
o May lie on 1 side of midline, side-by-side or one on top of the other
Ureter of displaced kidney crosses to opp side across midline
o Both kidneys may be displaced to opp side Æ ureters cross ea o at midline
x Abnormal Rotation
o Non-rotation: hilum is directed anteriorly
o Incomplete rotation: hilum directed anteromedially
o Reverse rotation: hilum directed anterolaterally
o Congenital Polycystic Kidney: failure of excretory tubules of metanephros to est contact
with collecting tubules = cysts Æ press upon normal renal tissue and destroy it
Cysts may also be derived from abnormally developed collecting tubules
o Aberrant Renal Arteries: kidney may receive blood supply partially or entirely from
arteries at an abnormal level
Non-ascent or incomplete ascent Æ aberrant arterys may constitute only supply
Aberrant artery may be only source of blood supply to a segment of the kidney
and may press upon ureter = obstruction Æ hyronephrosis
x Multiple Anomalies: 2+ anomalies may coexist; anomalies of position assoc with rotation
Absorption of Lower Parts of Mesonephric Ducts into Cloaca

x Lower ends of mesonephric ducts open into part of cloaca that forms UGS
x Utreteric buds arise cranially to cloaca from mesonephric ducts
x Parts of mesonephric ducts caudal to origin of ureteric buds absorbed into vesico-urethral canal
o Mesonephric ducts & ureteric buds now have separate openings into cloaca
o Openings of ureteric buds move cranially & laterally due to cont’d absorption of buds
o Triangular area (dorsal wall of v-u canal) bt openings of ureteric buds and those of
mesonephric ducts derived from absorbed ducts Æ mesodermal origin
Development of Ureter
x From part of ureteric bud that lies bt pelvis of kidney & vesico-urethral canal
x Ureter may be partially or completely duplicated Æ could lead to duplication of kidney
x Rare Æ >2 ureters on 1 kidney or both sides Æ 1 will open to bladder and other to abnormal site
x Ureter may end at abnormal sites
o ƃprostatic urethra, ductus deferens, seminal vesicles or rectum
o ƂXUHWKUDYDJLQDYHVWLEXOHUHFWXP
x Upper end of ureter may be blind (not connected to kidney)
x Hydroureter: ureter may be dilated due to obstruction of urine flow
x Ureter may have valves or diverticula
x Right ureter may pass behind IVC, then hooks around left side of IVCÆ kinking & obstruction
Development of Urinary Bladder

x Epithelium develops from cranial part of vesico-urethral canal (endoderm)
x Epithelium of trigone from absorbed mesonephric ducts (mesoderm)
x Muscular & serous walls of organ derived from splanchnopleuric mesoderm
3
x Developing bladder continuous cranially with allantois

x Allantois atrophies and is seen in postnasal life as fibrous band, urachus Æ extends from apex
of bladder to umbilicus
x Bladder may be absent or duplicated
x Sphincter vesicae may be absent
x Lumen of urinary bladder may be divided into compartments by septa
x Hourglass bladder: Bladder may be divided into upper & lower bc constriction of middle organ
x Bladder may communicate with the rectum
x Ectopia vesicae: lower part of anterior abdominal wall & ventral wall of bladder may be missing
o Cavity of bladder may be exposed on surface of body; usually assoc with epispadias
o Caused by failure of meso to migrate into lower abdominal wall (bt umbilicus & genital
tubercle) Æ may be due to excessive devl’t of cloacal mbrn
o Ectoderm of ant abd wall & endoderm of ventral wall of urinary bladder remain
unsupported & thin Æ rupture leads to exposure of cavity of urinary bladder
x Congenital diverticula may be present Æ found at junc’n of trigone with rest of bladder
Development of Urethra
x Female Æ caudal part of vesico-urethral (endoderm)
o Posterior wall from mesonephric ducts (mesoderm)
o Slight contribution from pelvic part of UGS
x Male
o Caudal part of vesico-urethral canal (endoderm) Æ urethra from bladder to ejac ducts
o Posterior wall derived from absorbed mesonephric ducts (mesoderm)
o Prostatic urethra & membranous urethra Æ pelvic part of definitive UGS
o Penile urethra (except terminal part) Æ epith of phallic part of definitive UGS
o Terminal part of penile urethra lies in glans Æ ectoderm
x Obstruction to urethraat junc’n with bladder
x Urethra may show diverticula
x May be duplicated entirely or partly
x Urethra may have abnormal comm. w/ rectum, vagina or ureter
x Hypospadias & Epispadias
Development of Prostate
x Devl’ps from lg number of buds that arise from epith of prostatic urethra (ie: from caudal part of
vesico-urethral canal & pelvic part of definitive UGS) Æ secretory epithelium of gland
x Inner glandular zone: buds that arise from emsodermal part of prostatic urethra
o Affected in senile hypertrophy of organ
x Outer glandular zone: buds from rest of prostatic urethra (endoderm)
o differentiates earlier than inner; in later life Æ site of carcinomatous change
x muscle & CT of gland derived from surr mesenchym which also forms capsule of the gland
x secretory elements of prostate are rudimentary at birth Æ development at puberty
x progressive atrophy in old age Æ may undergo benign hypertrophy or may be absent (rare)
x Female Homologs of Prostate
o Endodermal buds, similar to those in prostate can be seen in female
o Buds from caudal part of vesico-urethral canal Æ urethral glands
o Buds from UGS Æ paraurethral glands of Skene
4
Paramesonephric Ducts
x Present in intermediate mesoderm
x Formed by invagination of coelomic epithelium
x Lateral to mesonephric ducts in cranial part of nephrogenic cord
x When traced caudally Æ cross to medial side of mesonephric ducts
o Ducts of 2 sides meet & fuse in midline Æ utero-vaginal canal (uterine canal)
o Caudal end of uterine canal comes in contact w/ dorsal wall of definitive UGS
o ƂÆ uterine tubes, uterus & superior 2/3 of vagina
x ƃ Æ paramesonephric ducts remain rudimentary
o Greater part of each duct eventually disappears
o Appendix of testis: small rounded body att to testis that remains at cranial end of ea duct
x may occasionally give rise to cysts
o prostatic utricle = homolog to vagina (and maybe part of uterus)
Development of Uterus & Uterine Tubes

x Epithelium of uterus devl’ps from fused paramesonephric ducts
x Myometrium from surrounding mesoderm Æ as thickens, unfused horizontal parts of 2
parameonephric ducts Æ partially embedded w/in substance Æ fundus of uterus
x Cervix = separate region; Fettus Æ cervix is larger than body of uterus
x Uterine tubes from unfused parts of paramesonephric ducts; original points of invagination of
ducts into coelomic epith = abdominal openings of tubes Æ Fimbria
x Anomalies of Uterus
o Uterus Didelphys: Uterus may be completely or partially duplicated
o Lumen partially or completely subdivided by septum
o Entire uterus may be absent
o Unicornuate Uterus: one half of uterus may be absent
o Uterus may remain rudimentary
o Atresia of lumen in body or cervix
x Anomalies of Uterine Tube
o may be absent on one or both sides
o tubes may be partially or completely duplicated on one or both sides
o atresia of tubes
Development of Vagina
x lower end of utero-vaginal canal comes in close contact w/ dorsal wall of part of UGS
x vaginal plate Æ separates utero-vaginal canal & UGS
o vagina Æ development of lumen w/in vaginal plate
o sinovaginal bulbs: 2 swellings formed by prolif of endodermal cells of UGS
o bulbs fuse together = one mass Æ vaginal plate
o part of vaginal plate near future cervix derived from meso cells of utero-vaginal canal
x hymen situated at junc’n of lower end of vaginal plate w/ UGS; both surfaces lined by endoderm
x Vagina may be duplicated Æ usually assoc with duplication of uterus
x Lumen may be subdivided longitudinally or transversely by a septum
x Vagina may be absent; condition may or may not be assoc with absence of uterus
x Hymen may be imperforate
x Rectovaginal fistula: vagina may have abnormal comm. w/ rectum
x Vesicovaginal fistula: vagina may have abnormal comm. with bladder
5
Development of External Genitalia

x With formation of urorectal septum, cloacal mbrn becomes subdivided into a ventral, UG mbrn
& a caudal anal membrane
x UG mbrn becomes elongated in a cranio-caudal direction
x Mesoderm on either side of UG mbrn is soon heaped up Æ 2 longi elevations & 3 other elev’ns
o Primitive urethral folds (2)
o Genital tubercle: situated in midline bt urogenital mbrn and lower part of ant abd wall
o Genital swellings (Right & Left)
x Female External Genitalia
o Clitoris Æ formed when genital tubercle becomes cylindrical
o Labia major Æ formed by enlargement of genital swellings
o Posterior commissure Æ formed by midline fusion of posterior ends of labia majora
o UG mbrn breaks down = continuity bt UGS (=vestibule) & exterior
Labia minora Æ formed by primitive urethral folds; lined outside by ectoderm &
endoderm on inside
o Clitoris may be absent, bifid or may be double; may be enlarged in hermaphroditism
o Labia minora may show partial fusion
o Urethra may open on anterior wall of vagina (equiv to male hypospadias)
x Male External Genitalia
o Phallus: genital tubercle becomes cylindrical
o Penis: formed by enlargement of phallus
o Coronary sulcus allows distinguishability of glans as phallus grows
o Prepuce: formed by reduplication of ectoderm around distal part of phallus
o UG mbrn lies in linear grown & is flanked on either side by primitive urethral folds
As phallus grows, groove elongates & extends onto its under-surface (lined by
ectoderm) Æ primitive urethral groove
Phallus closely related to endodermal lining of phallic part of UGS Æ
endodermal cells grow and proliferate into phallus Æ urethral plate
Cells of urethral plate in contact w/ ectod cells lining primitive urethral groove
o UG mbrn breaks down Æ phallic part of UGS opens to outside in caudal part of groove
o Cells forming core of urethral plate degenerate along with ectodermal cells lining
primitive urethral groove Æ deeper groove Æ definitive urethral groove
o Definitive urethral groove lined by endodermal cells, formed on under-surface of
phallus – at base, groove is cont’s w/ cavity of UGS
Definitive urethral folds: margins of definitive urethral groove; approach and
fuse w/ eo Æ begins posteriorly in region of UGS & extends fwrds onto phallus
Penile urethra formed by fusion of folds; wall made up of:
x Original endodermal lining of phallic part of UGS
x Endodermal cells of urethral plate
x Extends only up to glans penis; the distal-most part of urethra is of
ectodermal origin & is formed by canalization of solid mass of ecto cells
o Scrotal sac: formed by midline fusion of genital swellings w/ eo; testes descend into here
o Entire penis may be absent or corpora cavernosa or prepuce may be missing
o Phimosis: opening of prepuce may be too narrow to allow retraction
o Penis may be double or bifid
o Penis may lie posterior to scrotum (very rare)
o Urethral folds may fail to fuse partially or completely
6
Hypospadias: complete failure to fuse Æ scrotum is in 2 halves and genitals look

like female’s; defect is confined to anterior part of phallus Æ urethra opens on
undersurface of penis
o Epispadias: urethra opens on dorsal aspect of penis Æ usually assoc with ectopia
vesicae; genital tubercle is formed caudal to UG mbrn instead of ventral to it
When mbrn ruptures, UGS opens cranial to developing penis
Prenatal Diagnosis of Sex

x 3-4 months Æ genitle tubercle is equally developed in both male and female; ultrasound can be
misleading bc clitoris can be mistaken for penis
Primordial Germ Cells

x Cells of ovaries and testes from which germ cells are formed Æ segregated in early embryo
x Differentiate in wall of yolk sac & migrate to region of developing gonads
x All spermatozoa & ova that are formed throughout life are believed to arise from PGCs
x PGCs have an inducing effect on gonad Æ req’d in order for gonads to develop
Development of Testes
x Develops from coelomic epithelium that covers medial side of mesonephros
x Genital ridge: region where testis is to devl’p Æ germinal epithelium becomes thickened
x Sex cords: formed by prolif’n of cells of germinal epith Æ grow into underlying mesenchyme
x Medullary cords: sex cords reach deep into gonad
x Seminiferous tubules: cords become canalized
o PGCs migrate to genital ridge and get incorporated in seminiferous tubules
x Interstitial cells from sex cords that are NOT canalized; some also from surr mesenchyme
x Tunica albuginea: dense layer of fibrous tissue formed by mesenchymal cells around region
o Completely separates sex cords from germinal epithelium Æ epith can no longer make
any contribution to testicular tissue
x Testis may be absent on one or both sides
x Testis may be duplicated
x 2 testes may be fused together
x Cyrptorchidism: anomalies of descent Æ descent may fail to occur or may be incomplete;
organ may lie in lumbar region, iliac fossa, inguinal canal or in upper part of scrotum
o Testis may complete its descent after birth
o Spermatogenesis often fails to occur in undescended testis
o Undescended testis is more likely to devl’p a malignant tumor than a normal testis
o Condition can be surgically corrected
x Ectopia: abnormal positions
o Under skin of lower part of abdomen
o Under skin of front of thigh
o In femoral canal
o Under skin of penis
o In perineum behind the scrotum
x Hermaphroditism
Duct System of Testes

x Some of the mesonephric tubules near the testis do not degenerate Æ duct system of testis
7
x Rete-testes: formed by anastomosis of seminiferous tubules w/ eo

x Vasa efferentia: formed when rete-testes est contact with persisting mesonephric tubules
x Epididymus: formed when cranial part of mesonephric duct becomes highly coiled on itself
x Ductus deferens: formed by distal part of mesonephric duct
x Seminal vesicle: on either side, as diverticulum from lower end of mesonephric duct
x Ejaculatory duct: formed by part of mesopnephric duct that lies bt its opening into prostatic
urethra and origin of seminal vesicle diverticulum
x Seminiferous tubules may fail to establish connection with vasa efferentia
x Ductus deferens may be absent entirely or partly on one or both sides
x Ductus deferens may have no connection with epididymus
Descent of Testes
x Develop in relation to lumbar region of posterior abdominal wall
x Fetus Æ gradually descend to scrotum
x 3rd month Æ reach iliac fossa & lie at site of deep inguinal ring
x 7th month Æ pass through inguinal canal
x 8th month Æ testis in scrotum by end of the month
x Factors that assist descent of testes
o Differential growth of body wall
o Formation of inguinal bursa
6th month Æ various layers of abd wall show outpouching twrds scrotum
Pouch progressively increases in size & depth Æ reaches bottom of scrotal sac
Descending testis enters pouch to reach scrotum
Cavity of inguinal bursa becomes inguinal canal and the various layers of its
wall forme the coverings of the testis and spermatic cord
o Gubernaculum: band of mesenchyme that extends from lower pole of testis to scrotum
Reaches bottom of inguinal bursa
When embryo increases in size, gubernaculum does NOT undergo a
corresponding increase in length Æ relative shortening of gubernaculum = testis
assumes a progressively lower position
Helps dilate inguinal bursa
Provides cont’s pathway for descending testis
o Processus Vaginalis: diverticulum of peritoneal cavity; actively grows into gubernacular
mesenchyme of inguinal canal & scrotum
As testis descends, it invaginate the processus vaginalis from behind
After descent done, loses all connection w/ peritoneal cavity Æ tunica vaginalis
Inguinal Hernia: abdominal contents may enter bc part that extends from deep
inguinal ring to tunica vaginalis may not disappear
x Congenital hernia
x Funicular hernia
x Infantile hernia
x Interstital hernia
Hydrocoele: fluid may accumulate in same area
x Congenital hydrocoele
x Vaginal hydrocoele
x Hydrocoele of cord
x Infantile hydrocoele
8
o Descent greatly influenced by hormones secreted by pars anterior of hypophysis cerebri
Vestigial structures in Region of Testis

x Any one of these may enlarge to forma a cyst
x Hydatid of Morgagni Æ Appendix of testis
x Appendix of epididymus
x Superior aberrant ductules
x Inferior aberrant ductules
x Paradidymis
Development of Ovary
x Genital ridge: Coelomic epith on medial side of mesonephros becomes thickened
x Sex cords & medullary cords proliferate from germinal epithelium & grow into mesoderm
x PGCs migrate to region of developing ovary and give rise to oocytes
x Primordial follicle: Sex cords become broken up into small masses Æ ea mass surr 1 PGC
x Medullary sex cords undergo regression in ovary Æ replaced by cortical cords which arise from
coelomic epithelium Æ give rise to Follicular cells
x Interstitial gland cells differentiate from mesenchyme of gonad
x No tunica albuginea is formed Æ germinal epith may contribute to ovary in postnatal life
x Descent of Ovary
o Descends from lumbar region Æ true pelvis
o Gubernaculum extends from ovary to laium majus Æ becomes att to developing uterus
at junc’n w/ uterine tube
Round Ligament of Ovary: part that persists bt ovary & uterus
Round Ligament of Uterus: part bt uterus and labium majus
x Ovary may be absent on one or both sides
x Ovary may be duplicated
x Ovary may descend into inguinal canal or even labium majus
x Adrenal or thyroid tissue may present in ovary; sometimes contains cells that are capable of
differentiating into various tissues Æ bone, cartilage, hair & growth of these cells Æ teratoma
Fate of Mesonephric Duct & Tubules in Male

x Mesonephric Duct gives rise to the following structures:
o Ureteric buds Æ ureters, pelves, calyces & collecting tubules of kidneys
o Trigone of bladder
o Poster wall of part of the prostatic urethra, cranial to openings of ejaculatory ducts
o Epididymus
o Ductus deferens
o Seminal vesicles
o Ejaculatory ducts
o Mesodermal part of prostate
o Appendix of epididymus: small rounded structure att to head of epididymis
Reps cranial end of mesonephric duct; occasionally may give rise to a cyst
x Remnants of Mesonephric Tubules
o Some persist to form vasa efferentia
o Some Æ vestigial structures Æ may give rise to cysts
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Superior aberrant ductules (epigenital tubules) – lie cranial to vasa efferentia;

connected to testis but NOT epididymis
Inferior aberrant ductules – caudal to vasa efferentia; connect epididymus only
Paradidymis: consists of tubules that lie bt testis & epididymis (paragenital
tubules), not connected to either of them
Fate of Mesonephric Ducts and Tubules in Female

x Derivatives are the same as male + posterior wall of female urethra
x Do NOT establish any connection with developing ovary; but DO give rise to some vestigial
structures seen in broad ligament near ovary
o Epoophoron: consists of a longitudinal duct running parallel to uterine tube & several
transverse ductules that open into the longitudinal duct (aka Gartner’s duct)
Corresponds to vasa efferentia & epididymus in males
Gartner’s duct is unusually long Æ runs along side of uterus Æ embedded in
wall of cervix; never opens into uterine lumen (equiv to male ductus deferens)
o Paroophoron: small blind tubules bt ovary & uterus (female equiv to paradidymis)
Control of Differentiation of Genital Organs

x Organs derived from same primordia in both sexes
x Male & female genital systems are identical until the beginning of 7th week
x Factors that determine if organs will devl’p as male or female
o XX Æ female
XY Æ male
o SRY gene on short arm of Y chromosome Æ testis determining factor
Vital role in causing developing gonad to become testis
Direct action on gonad + influences other genes (SOX-9)
x Sertoli cells formed from cells of sex cords
x Leydig cells formed from mesenchymal cells of gonadal ridge
o Once testis are formed, Leydig (interstitial) cells begin to produce testosterone under
influence of gonadotropins that are formed in the placenta
Testosterone influences differentiation of genital ducts & external genitalia
End of 18th week Æ fetal Leydig cells disappear; reappear @ puberty
o Sertoli cells
Mullerian inhibiting substance Æ causes regreassion of paramesonephric ducts
Androgen binding factor Æ formation of spermatozoa from speramtogonia
Hermaphroditism
x Hermaphrodite: person is both male and female
x True hermaphrodite: person has both testes and ovaries
o Person has at least one testis & one ovary
o External genitalia may be male or female or midway
o Chromosomal sex may be either male or female
x Pseudohermaphrodite: external genitalia look like those of one sex, & internal look like other
o Gonads are of one sex while genitalia (internal, external or both) are of opposite sex
o If patient has testis Æ male hermaphrodite
o If patient has ovary Æ female hermaphrodite
Caused by adrenogenital syndrome Æ excess of androgens produced by fetal
suprarenal gland; or by admin of progestins to mother during pregnancy
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Structure Male Derivative Female Derivative

Gonad Testis Ovary
Sex cords Sertoli cells Granulose cells
Seminiferous tubules
Primordial Germ Cells Spermatozoa Ova
Paramesonephric Duct Appendix of testis Uterine tube
Utricle of prostate Uterus
Upper 2/3 of vagina
Mesonephric Duct Appendix of epididymis Appendix of ovary
Epididymis Gartner’s duct
Ductus deferens
Ejaculatory duct
Seminal vesicle
Mesonephric tubules Vasa efferentia Eppophoron

Paradidymis Paroophoron
Genital Tubercle Penis Clitoris
Genital Swellings Scrotum Labia majora
Urethral Folds Floor of penile urethra Labia minora
Timetable of Events

3rd week Formation of intermediate mesoderm
External genitalia begin to form
4th week Pronephric tubules begin to form and have regressed by end of same week
Mesonephric tubules start forming
Urorectal septum begins to form
5th week Metanephros is formed
th
6 week Mesonephros is well-developed
Cloacal mbrn divides into urogenital & anal membranes
7th week Urogenital sinus is established
rd
3 month Urethral folds fuse with each other
At end of month, prostate begins to develop
12th week Definitive kidney (metanephros) becomes functional
5th month Vagina gets canalized
External genitalia are most susceptible to teratogens bt 7th & 9th weeks; but can still be affected later
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The Nervous System
x Ependymal
x Mantle Æ basal lamina (ventral) & alar lamina (dorsal) sep by sulcus limitans
o Alar lamina
Spinal cord Æ posterior grey colomn
Medulla, pons & midbrain Æ afferent nuclei
Myencephalon Æ olivary (migrate ventrally) & pontine nuclei (pons)
Metencephalon Æ cerebellum
Mesencephalon Æ colliculi, red nucleus & substantia nigra
o Basal lamina
Spinal cord Æ ventral grey column
Medulla, pons & midbrain Æ efferent cranial nerve nuclei
x Marginal Æ white matter
Neural Tube & its Subdivisions

x Prosencephalon
o Diencephalon Æ thalamus, hypoth, optic stalk, pars nervosa of pituitary
o Telencephalon Æ cerebral hemi (incl corpus striatum); R & L telencephalic vesicles
x Mesencephalon Æ midbrain
x Rhombencephalon cavity Æ 4th ventricle
o Metencephalon (cranial) Æ pons & cerebellum
o Myelencephalon (caudal) Æ medulla oblongata
x Flexures
o Cervical flexure: junc’n of rhombencephalon & spinal cord
o Mesencephalic (cephalic) flexure: midbrain region
o Pontine flexure: middle of rhombenceph Æ div into metencephalon & myencephalon
o Telencephalic flexure: occurs much later bt telencephalon & diencephalon
x Cavities
o Telencephalic vesicles Æ lateral ventricle
o Diencephalon + central part of telencephalon Æ 3rd ventricle
o Mesencephalon Æ cerebral aqueduct
o Rhombencephalon Æ 4th ventricle Æ continues in spinal cord as central canal
Neural Crest
x Neurons of spinal posterior (dorsal) nerve root ganglia
x Neurons of sensory ganglia of CN 5, 7, 9, 10
x Neurons & satellite cells of sympathetic ganglia, preaortic ganglia
x Neurons & sat cells of parasymp ganglia of CNs (ie: ciliary, submadibular, sphenopalatine, otic)
x Parasymp ganglia (enteric ganglia) of GIT & ganglia of pelvic viscera
x Schwann cells
x Specific cells of adrenal medulla
x Chromaffin tissue
x Melanoblasts of skin
x Pia-mater & arachnoidmater
x Mesenchyme of dental papilla, odontoblasts & dentine
1
x Bones of face & part of vault of skull (frontal, parietal, squamous temporal, sphenoid,
maxilla, zygomatic, nasal, vomer. Palatine, mandible)
x Dermis, smooth muscle & fat of face & ventral aspect of neck
x Muscles of ciliayr body
x Sclera & choroid of eye
x Substantia propria & posterior epithelium of cornea
x CT of thyroid, parathyroid, thymus & salivary glands
x Derivatives of 1st, 2nd & 3rd pharyngeal cartilages
x C cells of thyroid gland
x Cardiac semilunar valves & conotruncal septum (spiral + bulbar septum)
x Hirschsprung’s disease, aorticopulmonary septal defects of heart, cleft lip/palate,
frontonasal dysplasia, neurofibromatosis, tumors of adrenal medulla, albinism…
Spinal Cord
x Ependymal
x Mantle Æ basal lamina (ventral) & alar lamina (dorsal) sep by sulcus limitans
o Grows faster in ventral part of neural tube and becomes thicker than dorsal part
o Alar lamina Æ posterior grey colomn Æ sensory structures (ie: interneurons)
o Basal lamina Æ ventral grey column Æ motor structures
o Posterior median septum formed when dorsal part of cavity obliterated
o Ventral part of cavity Æ central canal
o Anterior median fissure: formedd by further enlargement of basal lamina Æ projects
forwards to either side of midline = furrow, fissure bt projecting basal laminae of 2 sides
x Dorsal nerve roots formed by axons of cells that devl’p from neural crest
x Dorsal nerve root ganglia: grps of nerve roots that collect on dorsolateral aspect of spinal cord
o Central processes Æ spinal cord Æ dorsal nerve roots
o Peripheral processes Æ sensory components of spinal nerves
x Marginal Æ white matter
o Ascending tracts: axons of neurons in posterior grey column enter marginal layer
o Descending tracts: axons of cells devl’ping in brain grow downwards
x Full term Æ lower end of cord is at L3 (vertebral column elongates more than spinal cord)
x Adult Æ spinal cord usually ends L1 (lower border)
x After birth Æ recession of spinal cord cont’s Æ intervertebral foramina no longer lie at level
where corresponding nerves emerge from spinal cord
Medulla Oblongata
x Sulcus limitans divides ea lateral wall Æ dorsal (alar) lamina & ventral (basal) lamina
x Cells developing in lateral part of each alar lamina migrate ventrally & reach marginal layer
overlying ventrolateral aspect of basal lamina Æ bulbo-pontine extension Æ olivary nuclei
x Gracile & cuneate nuclei derived from lower-most part of somatic afferent column
Pons
x Cranial part of bulbo-pontine extension also contributes to pons Æ pontine nuclei
x Axons of pontine nuclei grow transversely Æ middle cerebellar peduncle
x Rhombic lip: lateral part of alar lamina Æ specialized = cerebellum
x Ventral part of alar lamina Æ sensory cranial nerve nuclei of pons
x Basal lamina Æ motor cranial nerve nuclei of pons
2
x Ventral part of pons

o Middle cerebellar peduncle
o Corticospinal & corticobulbar fibers descend from cerebral cortex & pass through ventral
pons en route to medulla & spinal cord; some fibers from cerebral cortex terminate in
relation to pontine nuclei Æ corticopontine fibers
Midbrain
x Basal lamina
o Occulomotor nerve nucleus, Trochlear nerve nucleus, Edinger Westphal nucleus (GVE)
x Alar lamina Æ cells of colliculi; red nucleus & substantia nigra
x Marginal layer of ventral part of mesencephalion invaded by downward growing fibers of
corticospinal, corticobulbar & cortico-pontine pathways Æ basis pedunculi
Cerebellum
x From dorsolateral part of alar lamina of metencephalon
x R & L primordial extend medially in roof plate Æ fuse across midline
x Intraventricular part: bulges into cavity of developing 4th ventricle
x Extraventricular part: bulging on surface; later constitutes almost the whole of organ
x some cells of mantle layer migrate into marginal layer Æ cerebellar cortex
x other cells Æ dentate, emboliform, globose, fastigal nuclei
x superior cerebellar peduncle: axons growing out of dentate nucleus
x middle cerebellar penduncle: axons growing into cerebellum from cells of pontine nuclei
x inferior cerebellar peduncle: fibers that grow into cerebellum from spinal cord & medulla
Cerebral Hemisphere
x from lateral telencephalic vesicles of prosencephalon
x Telencephalic vesicles Æ cerebral cortex & corpus striatum
x Diencephalon Æ thalamus, hypothalamus & related structures
x Telencephalon grows and completely covers lateral surface of diencephalon Æ cerebral cortex &
corpus striatum lie lateral to thalamus & hypothalamus
x Cavity of diencephalon Æ 3rd ventricle
x Cavities of telencephalic vesicles Æ lateral ventricles
o Spherical Æ elongated
o Temporal lobe formed by downwards and forwards growth of posterior end of t vesicle
Cavity Æ inferior horn Æ lateral ventricle becomes C-shaped
o Backward growth Æ occipital pole
Cavity Æ posterior horn
x Growth of t vesicles Æ medial walls become apposed to eo Æ surfaces continuous with eo in
floor of groove bt them = roof of 3rd ventricle
x Choroid fissure: lateral invagination of medial wall into lateral ventricle
o Telachoroidea: formed by fold of pia mater that extends into fissure
o Choroid plexus: bunch of capillaries that formes within fold; ependymal covering
formed by the original wall of ventricle
o Becomes C-shaped after temporal pole & inferior horn are formed
o Inferior part of fissure invaginates into inferior horn of lateral ventricle
Thalamus & Hypothalamus

x Epithalamic & hypothalamic sulci divide diencephalon into 3 regions
3
x Central region Æ thalamus

x Above epithalamic sulcus Æ epithalamus (small) Æ habernular nuclei & pineal body
x Below hypothalamic sulcus Æ hypothalamus
x Nuclei of hypoth & thalamus formed by multiplication of cells in mantle layer of diencephalon
Corpus Striatum
x Formed by cells in mantle layer
x Medial & lateral subdivisions
x Internal Capsule: Axons that are growing downwards from cerebral cortex of going towards
cortex pass thru corpus striatum Æ divided into deep & superficial parts
o Caudate Nucleus: deep to internal capsule
o Lentiform Nucleus: superficial Æ putament, globus pallidus
Cerebral Cortex
x Formed by migration of cells from mantle Æ marginal layer
x Full term Æ several layers of cells
x Thickening and side-to-side expansion of cortex = increased surface area (faster than hemis)
x Folding = sulci & gyri
x Hippocampal cortex Æ hippocampus & indusium griseum; devl’ps in medial wall of telenceph
o Follows curve of choroid fissure & assumes ring-like config’n
o Superior part separated from fissure by formation of corpus callosum Æ insdusium gris.
o Lower part develops more Æ hippocampus & dentate gyrus
o Structures pushed into cavity of inferior horn of lateral ventricle by growth of neocortex
x Pyriform cortex Æ olfactory sensations; marginal layer of telen, superificial to corpus striatum
o Uncus
o Anterior part of parahippocampal gyrus
o Anterior perforated substance
x Neocortex Æ expands greatly = whole of cerebral cortex that’s seen on superolateral & medial
surfaces of cerebral hemisphere & cortex of inf surface (excl pyriform); superolat of teleneph
White Matter of Cerebrum

x Axons of cortical cells that grow twrds other areas of cortex w/in same or opposite hemisphere
x Axons of cortical cells that grow dwnwrds thru hemi Æ brain & spinal cord
x Axons that connect thalamus, hypothalamus & basal ganglia to one another & to cortex
x Axons that grow into hemisphere from brainstem & spinal cord
Cerebral Commissures
x Lamina terminalis: part of wall of neural tube that closes cranial end of prosencephalon
o In anterior wall of 3rd ventricle after appearance of telencephalic vesicles
o Any neurons growing from one hemi to the other must pass through lamina
x Commissural plate: formed when lamina terminalis becomes thickened
x Anterior Commissure
x Hippocampal Commissure
x Corpus callosum: rapidly increases and extends bkwrds & roofs over anterior diencephalon
x Optic chiasma
x Habernular commissure
x Posterior commissure
4
Anomalies of Brain & Spinal Cord

x Non-closure of Neural Tube
o Posterior rachischisis: whole length of neural tube remains unclosed
o Anencephaly: neural tube stays open in region of the brain, exposed tissue degenerates
o Cranium bifidum: non-closure of cranium
o Spina bifida: non-closure of vertebral canal
x Outward Bulging of Neural Tube & Covering Membranes
o Non-fusion of neural tube or overlying bones (ie: spina bifida) Æ neural tissue lies
outside cranial cavity or vertebral canal
o Encephalocoele: occurs in region of brain
o Myelocoele: occurs in spinal region
o Non-closure of neural tube Æ tissue exposed on surface (anencephaly & rachischisis)
o Meningo-mylocoele: closure of neural tube, but bulging due to defect in overlying
bones Æ neural tissue is covered by bulging skin & mbrns
Medulla oblongata & tonsils of cerebellum displaced caudally into foramen
magnum Æ obstructs CSF Æ hydrocephalus Æ Arnold Chiari deformity
o Meningocoele: bulging caused by membranes alone; neural tissue is normal
x Congenital Hydrocephalus
o Hydrocephalus: abnormal amount of CSF accumulates in ventricular sys of brain
Ventricles become very large Æ baby has big head
Pressure of fluid = degeneration of nervous tissue
o Hydromyelia: enlargement of spinal cord
o Syringocoele: enlargement of central canal
o Syringomyelia: formation of abnormal cavities near central canal Æ nerv tiss destroyed
o Dandy Walker Syndrome: blockage of median & lateral apertures of 4th ventricle;
enlargement of posterior cranial fossa & abnormal cerebellum
o Stenosis or malformations of cerebral aqueduct may also obstruct flow of CSF
x Faulty Development
o Microcephaly: brain too small
o Macrocephaly: brain too large
o Gyri may not or are poorly formed
o Cerebral cortex doesn’t devl’p normally Æ impaired intel or congenital paralysis
x Absence of Parts of Nervous System
o Corpus callosum, spinal cord or cerebellum could be absent
Sympathetic Neurons
x Preganglionic Neurons: devl’p in mantle layer of T1 – L2/3
o Near sulcus limitans Æ lateral horn of spinal cord
o Myelinated axons Æ ventral roots Æ spinal nerves Æ postganglionic neurons
o Fibers that go to visceral sympathetic ganglia pass through branches of sympathetic trunk
to reach visceral ganglia
x Postganglionic Neurons: axons grow towards and innervate various viscera of body
o Some enter spinal nerves & distrib to BVs, hair & sweat glands
o Derived from neural crest cells
Parasympathetic Neurons
x Preganglionic from Cranial Parasympathetic Outflow
o Formed in relation to general visceral efferent nuclear column of brainstem
o Edinger-Westphal nucleus, salivatory & lacrimatory nuclei, dorsal nucleus of Vagus
5
o E-W nucleus Æ oculomotor nerve Æ ciliary ganglion

o Superior saliv & lacrim nuclei Æ facial nerve Æ sphenopalatine & submand ganglia
o Inferior salivatory Æ glossopharyngeal nerve & terminate in otic ganglion
o dorsal nucleus of Vagus Æ terminate in various ganglia in walls of viscera
x Preganglionic from Sacral Parasympathetic Outflow
o Formed in mantle layer of S2-S4
o Near sulcus limitants
o Terminate by synapsing with postganglionic neurons in walls of pelvic viscer & hindgut
x Postganglionic Neurons derived from Neural crest cells
o Cranial Æ ciliary, otic, submandibular & sphenopalatine ganglia
o Ganglia also in various viscera supplied by vagus nerve &
o Ganglia that are near hindgut & pelvic viscera (sacral outflow)
o Entire length of gut (esoph Æ anal canal) has postgangionic parasymp neurons
o Neural crest cells w/in gut Æ enteric nervous system
Timetable of Events
3rd week Neural tube begins to form

4th week Neural folds begin to fuse.
Premordia of sensory ganglia (spinal & cranial) are formed
25th day Closure of anterior neuropore
27th day Closure of posterior neuropore
28th day Most cranial pair of cervical spinal ganglia develops
5th week Formation of brain vesicle
Sympathetic ganglia formed
Cerebral hemispheres begin to form
8th week Cerebellum starts forming
10th week Corpus callosum forms
12th week Cerebellar cortex & purkinje cells are formed
15th week Dentate nucleus is seen
4th month Myelination of nerve fibers begin
Late fetal life Sulci & gyri appear over cerebral hemispheres
6

Hypophysis Cerebri, Pineal, Adrenal
Hypophysis Cerebri (pituitary gland)

x Developed from two separate sources
x Anterior and intermediate pts Æ devl’p from Rathke’s pouch (ecto diverticulum) that grows
upward from roof of stomatodaeum, in front of the buccopharyngeal mbrn Æ later cut off
x Pars nervosa and stalk Æ downgrowth from floor of 3rd ventricle (diencephalon) in
infundibulum Æ fuses with posterior part of Rathke’s
x Pars anterior & pars intermedia sep by Cleft of Rathke’s Pouch
o Anterior wall of Rathke’s Æ pars anterior of hypophysis
o Posterior wall of Rathke’s Æ remains thin and forms pars intermedia
x Tuberal part of hypophysisÆ cells of the ant pt grow upward along infundibular stalk
x After formation of mouth and pharynx, Rathke’s pouch lies in the roof of nasopharynx
o Craniopharyngiomas Æ remnants of pouch give rise to peculiar tumours
x Accessory ant lobe tissue may be seen near the post wall of pharynx
x Agenesis: hypophysis will fails to develop (rare)
x Hypoplasia: hypophysis is underdeveloped
x Rathke’s pouch appears in the 3rd WEEKÆ loses contact w/ surf epi by 2nd month
Pineal Gland
x Arises as a diverticulum from roof of the diencephalon
x At first hollow but later becomes solid
x Specific cells of pineal body are believed to be modified neuroglial cells
x Secrete a number of hormones that have a regulatory influence on other endocrine glands
Adrenal
x Consist of a superficial cortex and a deeper medulla
x Cortex Æ cells arise from coelomic epithelium (mesoderm)
o Cells from the angle btw developing gonads and att of mesentery
x Medulla Æ cells derive from neural crest (ectoderm)
o Cells similar to the postganglionic sympathetic neurons
o Preganglionic sympathetic neurons terminate in relation to them
o Cells migrate to the region around the developing cortical cells
x Cells from coelomic epithelium divide into 2 groups
o The first cells formed are large and acidophilic
Surround the medulla and form fetal cortex Æ disappears after birth
o Give rise to smaller cells that surround the fetal corex Æ definitive cortex
x Differentiation of cortical zones begins in late fetal period
o Zona glomerulosa and zona fasciculata are present at birth
o Zona retiularis becomes recognizable only at the end of 3rd year
x Suprarenal is same size in the fetus as in the adult
o Quite large compared to the fetal kidney
o Size of gland (particularly fetal cortex) becomes smaller during the 1st year
x Adrenal gland begins to develop in 5th week
x Adrenal cortical tissue may be present at various ectopic sites
x Entire adrenal may be ectopic and lie deep to the capsule of the kidney
1
o May be fused to the liver or the kidney

x Maybe congenital hyperplasia of the cortex
o Adrenogenital Syndrome Æ in males, early development of secondary sexual characters
o Pseudohermaphroditism Æ in females, enlargement of clitoris, child mistaken for male
Chromaffin Tissue
x Made up of cells similar to that of the adrenal medulla
o Also derived from neural crest
x Seen in relation to the abdominal aorta Æ forms paraaortic bodies
x Seen in relation to sympathetic ganglia and plexuses and along the splanchnic nerves
Timetable of Events

rd
3 week Infundibular diverticulum develops from the floor of the 3rd ventricle
4th week Rathke’s pouch projects from the roof of stomatodeum
5th week Adrenal gland begins to develop
8th week Rathke’s pouch loses its connection with the oral cavity
2

The Eye and Ear
Development of the Eye

x Various components of the eyeball derive from the primodia
o Optic vesicle Æ outgrowth from prosencephalon
o Lens placode Æ specialized area of the surface ectoderm Æ forms the lens
o Mesoderm surrounding the optic vesicle
Formation of the Optic Vesicle

1. Neural plate shows linear thickened area on either side Æ prosencephalon
2. Optic Sulcus Æ thickened area becomes depressed
3. Neural plate is converted into the prosencephalic vesicle
o Optic vesicle Æ wall of prosencephalon overlying sulcus bulges outward
4. Optic stalk Æ proximal part of optic vesicle that becomes constricted and elongates
Formation of the Lens Vesicle

1. Lens placode Æ area of optic vesicle that grows laterally & contacts surf ecto Æ thickens
2. Lens vesicle Æ lens placode sinks below the surface and is converted into vesicle
3. lens vesicle becomes completely separated from the surface ectoderm
Formation of the Optic Cup

x Optic cup Æ optic vesicle becomes double-layered bc there is differential growth of wall of
vesicle Æ margins of the cup grow over the upper and lateral sides & enclose lens
x Choroidal/fetal fissure Æ deficiency in growth of cup wall inferiorly – con’ts along optic stalk
x An ext of the mesoderm around neural tube (form meninges) covers the optic vesicle
o dura mater Æ superficial fibrous layer
o pia-arachnoid Æ Deeper vascular layer
x part of inner vascular layer is carried into cup through the choroidal fissure
Derivation of Parts of the Eyeball

1. Lens Æ formed from the lens vesicle
o Vesicle is first lined by a single layer of cubical cells
o Cells in ant wall stay the same, cells in post wall become elongated
o Cavity of vesicle is obliterated by the elongating cells
o Cells of post wall lose nuclei and converted into fibres of the lens
o Ant layer remains as epithelium covering this aspect of the lens
2. Retina Æ derived from the layers of the optic cup
o Optical part of retina Æ lg post pt of optic cup that become thick & forms retina proper
o Ciliary & iridial parts of retina Æ ant pt of optic cup is thin and forms the epithelial
covering for the ciliary body and iris
o Pigmented layer of retina Æ outer wall of post pt of optic cup that remains thin
o Inner wall of cup differentiates Æ matrix cell, mantle and marginal layers
i. Matrix layer Æ form rods and cones
ii. Mantle layer Æ bipolar cells, ganglion cells, neurons of retina & supporting
elements
iii. Marginal layer Æ layer of nerve fibres
iv. Optic nerve Æ the fibres pass through the choroidal fissure into the optic stalk
1
3. Vitreous Æ derived partly from ectoderm and partly from mesoderm

o Ectodermal part derived mainly from optic cup, but lens vesicle may contribute
o Mesodermal part passes through the choroidal fissure into the optic cup
4. Choroid Æ formed from the inner vascular layer of mesoderm that surrounds the optic cup
o Mesoderm may contain cells that derive from the neural crest
5. Ciliary body and iris Æ derived from a forward prolongation of meso forming choroid
o Post surf is lined by two layers of pigmented epithelium derived from the ciliary and
iridial parts of retina
i. Two layers correspond to the two layers of the optical cup
o Musculature of the iris Æ sphincter and dilator pupillae is of ecto origin (optic cup)
o Ciliary muscles Æ neural crest origin (generally regarded as mesodermal origin)
6. Sclera Æ formed from post pt of layer of meso surrounding the optic cup and dura
o some believe that the meso forming sclera is infiltrated by neural crest cells
7. Cornea Æ substantia propria and inner epithelium derive from neural crest (same as sclera)
o Substantia propia is in close contact w/ surf ecto that forms the epi covering superficial
surf of the cornea
8. Anterior and posterior chambers of eye Æ (aq chamber) formed by a splitting of the meso in
the region and correspond to the subarachnoid space of the brain
o Ant chamber formed by vacuolization of meso present ant to the lens
o Vacuolization splits mesenchyme into outer (ant) and inner (post) layers
i. Outer layer becomes continuous w/ sclera and w/ the substantia propria of cornea
ii. Inner layer lies in front of lens and iris and is termed pupillary membrane
o Meso cells lining the cavity give origin to a flattened mesothelium
9. Blood vessels of the eyeball Æ formed in the meso layer that is a con’t of the pia-arachnoid
o Pt of meso that invaginates the optic cup forms the retinal vessels
o Central a and v of retina 1st lie in the choriodal fissure, but then buried in optic nerve
o Central a of retina runs through the substance of the distal pt of the optic nerve
o Initially lens is covered by vascular capsule
i. Hyaloids a Æ supp post pt of capsule, cont’n of central a, passes through vitreous
1. Hyaloids and vitreous disappear, but hyaloids canal persist
ii. Ant pt of capsule comes to be lined post by the iridial pt and forms iris
o Iridopupillary membrane Æ pupil closed by a pt of vascular tissue, disappears bf birth
Part Derived from

Lens Surface ectoderm
Retina Neuroectoderm (optic cup)
Vitreous Mesoderm
Choroid Mesoderm (infiltrated by neural crest cells)
Ciliary body Mesoderm
Ciliary muscles Mesenchymal cells covering the developing ciliary body (neural crest)
Iris Mesoderm
Muscles of iris Neuroectoderm (from optic cup)
Sclera Mesoderm (infiltrated by neural crest cells)
Cornea Surf epi by ecto, substantia propria and inner epi by neural crest
Conjunctiva Surface epithelium
Blood vessels Mesoderm
Optic nerve Neuroectoderm, its coverings (pia, arachnoid and dura) are from meso
2
Accessory Structures of Eyeball

x Eyelids Æ replication of surf ecto above and below the cornea
o Ecto folds contain meso that give rise to muscle and to the tarsal plates
o Conjunctival sac Æ enlargement of folds where margins fuse together for a space
x Lacrimal gland Æ formed from buds that arise from upper angle of conjunctival sac
x Lacrimal sac and nasolacrimal duct Æ from ectoderm of naso-optic furrow
o Furrow lies along line of junction of maxillary process and lateral nasal process
o Extends from medial angle of eye and region of the developing mouth
o Lacrimal sac Æ upp pt of cord that is formed from furrow being buried in ecto
o Nasolacrimal duct Æ is lower part of cord, has secondary connection to nasal cavity
o Lacrimal canaliculi Æ canalization of ecto buds that arise from the margin of ea eyelid
Near its medial end and grow to the lacrimal sac
x Anophthalmos Æ eyeball fails to develop
x Microphthalmos Æ eyeball remains small
x Cyclopia Æ two eyes fuse together
x Synophthalmos Æ eyes fuse partially, form one midline organ
x Optic vessel may not be invaginated by the lens Æ remains a cyst
x Coloboma Æ choroidal fissure does not obliterate Æ deficiencies in various layers of the eye
o Iris, ciliary body and choroid
x Cornea may be absent, anomalies of size and shape, may show congenital opacities
x Blue sclera Æ sclera is thin and the pigment of the choroid can be seen
x Iris may show anomalies of its histological structure
o Rarely the sphincter or dilator pupillae muscle may be absent
o Pupil may be abnormal in position, size or shape
x Rarely the lens may be absent or be very small; May be abnormal in position or shape
o Cataract Æ congenital opacities of lens Æ due to parathyroid deficiency, avitaminosis
or infection of German measles during early pregnancy
x Persistent papillary membrane Æ vascular capsule of the lens persist and occludes the pupil
o Hyaloids artery, vascular capsule of lens, or their remnants can persist
x Albinism Æ various layers of the eye may show too little pigmentation
o Layers of the eye could also show too much pigmentation
x Retina may show various congenital anomalies of its structure
o Could involve the macula Æ visual defects including colour blindness
Anomalies of Accessory Structures of Eye

Eyelids and Related Structures
x Eyelids rarely absent Æ no conjunctival sac Æ conjunctiva and cornea are replaced w/ skin
x Coloboma of eyelid Æ part of the eyelid may be missing
o Underdevelopment of the tarsus or of the Meibomian glands
x Palpebral fissue may be abnormally wide or narrow Æ abnormal orientation and shape
o Two lids may be completely or partially fused
x Epicanthus Æ abnormal fold of skin in relation to the lids Æ normal in some races
x Entropion Æ lid margins are turned inwards
x Ectropion Æ lid margins are turned outwards (Rarely the whole lid may be inverted)
x Ptosis Æ lavatory palpebrae superioris may fail to develop Æ drooping of lids
x Eyelashes and eyebrows may be missing or duplicated
o Eyelashes may be abnormal in direction
3
Anomalies of the Lacrimal Apparatus

x Lacrimal gland may be absent or non-functional (may be ectopic)
x Lacrimal passage may be absent in whole or part or atresia of some part
x Lacrimal duct could be open furrow on face Æ non-obliteration of the naso-optic furrow
x Supernumerary puncta or canaliculi
Internal Ear
x Otic placode Æ thickening of surf ecto overlying the developing hindbrain Æ memb labyrinth
x Otic pit Æ otic placode become depressed
x Otic vesicle Æ otic pit become rounded and seperates from surface ectoderm
x Membranous labyrinth Æ differential growth of various pt of otic vesicle wall
o Give rise to specialized sensory end organs of hearing and of equilibrium
Cristae of semicircular ducts
Maculae of utricle and saccule
Organ of Corti of cochlea
o Innervated by peripheral processes of the cells of the vestibulocochlear ganglion
Derived form the neural crest Æ cells remain bipolar throughout life
x Bony labyrinth Æ formed from mesenchyme surrounding membranous labyrinth
x Otic capsule Æ mesenchyme becomes condensed Æ converted into cartilage
x Loose periotic tissue bt cartilage and membranous labyrinth
o Spaces of bony labyrinth created by disappearance of periotic tissue
x Endolymph Æ fluid that fills the membranous labyrinth
x Perilymph Æ fluid that fills the periotic spaces
x Vestibule Æ space where periotic tissue disappears around utricle and saccule
x Semicircular canals Æ space where periotic tissue disappears around semicircular ducts
x Two spaces are formed on either side of the cochlear duct
o Scala tympani Æ grows towards tympanic cavity from which it is separated by a membr
o Scala vestibuli Æ communicates with the vestibule
x The cartilaginous labyrinth becomes ossified to form the bony labyrinth
Middle Ear
x Tubo-tympanic recess Æ epithelia lining the middle ear and pharyngo-tympanic tube is derived
o Develops from the dorsal pt of 1st pharyngeal pouch and contribution from 2nd pouch
x Tympanic antrum and mastoid air cells are formed from extensions from middle ear
x Malleus and incus Æ derived from dorsal end of Meckel`s cartilage
x Stapes Æ derived from dorsal end of cartilage from 2nd pharyngeal arch
x Ossicles are 1st outside the mucous mbrn of developing middle ear
o Invaginate mucous mebrn which covers them throughout life
o Fully ossify in the 4th month of intrauterine life Æ 1st bones in the body to ossify
x Tensor tympani Æ derived from meso of 1st pharyngeal arch and stapedius from 2nd arch
External Ear
x External acoustic meatus Æ derived from dorsal pt of 1st ecto cleft
o Deeper pt formed from proliferation of lining epi which grows toward middle ear
o Meatal plug Æ when proliferation is solid Æ later canalized
x Pinna (auricle) Æ formed from 6 meso thickening called tubercles or hillocks
o Appear on mandibular & hyoid arches around opening of dorsal pt of 1st ecto cleft
4
x Mandibular arch forms only the tragus and sm area around it, rest formed from hyoid arch
o Consistent w/ the fact that auricular muscles are supplied by facial nerve
Tympanic Membrane
x Formed from apposition of the tube-tympanic recess and 1st ecto cleft
o Forming the inner (endodermal) and outer (ectodermal) epithelia linings of membrane
o Intervening mesoderm forms the CT basis
x Handle of malleus grows into CT from above
x Chorda tympani nerve 1st outside membrane, but later comes to lie w/in bc of upward ext
Anomalies of the Auricle

x Development of auricle may get arrested at any stage
o Result in being totally or partially absent, isolated nodules, or be very small or large
x Migration from its primitive caudo-ventral position may remain incomplete
o Migration occurs bc of growth of maxillary and mandibular processes
o Ex association of caudo-ventral displacement of auricle w/ mandibulofacial dystosis
Anomalies of the External Auditory Meatus

x Stenosis or atresia of meatus over its whole length or over part of it
o Lumen may be closed by fibrous tissue, by cartilage, or by bone
x Norm curvature of meatus may be accentuated Æ tympanic membr cannot be seen from outside
Anomalies of the Middle Ear

x Ossicles may be malformed, may show abnormal fusion to one another or to wall of middle ear
o Stapes may be fused to the margins of the fenestra vestibule
x Facial nerve may bulge into middle ear and follow an abnormal course
x Stapedial artery that disappears may persist
Anomalies of the Internal Ear

x Various pt of the membranous labyrinth may remain underdeveloped
o Some cases cochlea alone is affected
o These anomalies lead to congenital deafness
Timetable of Events
Eye
22nd day Appearance of optic sulcus (over the neural plate)
th
4 week Optic vesicle comes in contact w/ surface ectoderm
Lens placode is forming
5th week Eye primordium is completely surrounded by loose mesenchyme
6th week Choriod fissure is formed; Lens vesicle is seen
th
7 week A solid lens is formed
The eyeball is most susceptible to teratogens during the 4th to 8th week, and can get affected till the
end of pregnancy.
5

Ear
22nd day Otic placode is seen
th
5 week Auricle starts forming
th
6 week The cochlea and semicircular canals starts forming
th
8 week The cochlea and semicircular canal assume their definitive external form
th
10 week Scala vestibule and scala tympani appear
th
7 month External acoustic meatus gets canalized
The ear is most sensitive to teratogens during the 4th to 9th weeks, and can be affected up to the 12th
week.
6

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Embryology Dr.

Venkatesh Test 1: Chapters 1-6

Human Embryology – Chapter 1

Embryology: study of the devl’t of an individual before birth

Gonads & Gametes

x Chiasmata: point of adherence of crossing over

Human Embryology – Chapter 2

Structure of a Mature Spermatozoon

o Divide mitotically = Type A & Type B spermatogonia

o Ovum shed from ovary is not fully mature

Abnormalities in Formation of Gametes

o broad face, obliquely placed palpebral fissures, epicanthus,

Human Embryology – Chapter 3

Structure of the Uterus

Phases of the Mestrual Cycle

o Oestrogens produced by developing follicles = changes

Hormonal Control of Ovarian & Uterine Cycles

x Hypothalamus = major control center of reproduction

Human Embryology – Chapter 4

Formation of Germ Layers

1. Formation of endoderm Æ some cells of inner cell mass flattened

Alternative View of Formation of Germ Layers

x some cells of epi- migrate to primitive streak Æ mesoderm

Use of Stem Cells in Treatment of Diseases

Age (days) Developmental Events

Human Embryology – Chapter 5

x Primitive knot: enlargement of cranial end of primitive streak

o Lateral plate mesoderm

Formation of the Notochord

Formation of the Neural Tube - Neurulation

Subdivision of Intra-Embryonic Mesoderm

Formation of the Intra-Embryonic Coelom

Yolk Sac and Folding of Embryo

Effect of Head & Tail Folds on Positions of Other Structures

Timetable of Events in this Chapter

Age (days) Developmental Events

Allantoic diverticulum is seen

Human Embryology – Chapter 6

x Implantation: developing embryo gets attached to endometrium

Implantation Æ 6th day of fertilization

o firmly united to chorion

Formation of Chorionic Villi

Further Development of Placenta

Normal Site of Implantation of the Ovum

Abnormal Sites of Implantation of Ovum

o Ectopic Pregnancy: ovum gets implanted anywhere outside uterus

Mutual Relationship of Amniotic Cavity, Extra-Embryonic Coelom & Uterine Cavity

Age (days) Developmental Events

Human Embryology – Chapter 7

x Epithelia from ectoderm, endoderm OR mesoderm

x Proximal part of diverticula become canalized Æ duct system

Connective Tissue (CT)

x Hyaline cartilage Æ collagen fibers present, but can’t see easily

Bone Formation (bone derived from mesoderm)

Endochondral ossification: cartilage Æ bone (ie: long bones)

Development of a Typical Long Bone

Growth of a Long Bone

o Zone of dead cartilage cells Æ calcified Æ bone

Anomalies of Bone Formation

Formation of Neurons & Neuroglial Cells

Formation of Myelin Sheath

o PNS Æ derived from Schwann cells