Development of CNS

1. Differentiation of Neural Tube and Neural

Crest
2. Formation of Vesicles and Brain
Curvatures
3. Development of the Brain
4. Development of the Spinal Cord
5. Nervous System Malformations
1

Formation of the Neural Tube

Neurulation = formation of neural plate
+ formation of neural folds + closure
of the folds to form neural tube
completed by the end of the fourth
week
the embryo may be referred to as a
neurula.
2

Formation of the Neural

Tube
notochord induces the overlying embryonic
ectoderm to thicken and form neural
plate.
neural plate = an elongated plate of
thickened epithelial cells.
The ectoderm of neural plate
(neuroectoderm) gives rise to CNS.
5

Formation of the Neural

Tube
At first, it corresponds to the underlying notochord, in
length .
It appears dorsal to the notochord.
As the notochord elongates, the neural plate broadens
And eventually extends cranially as far as the
oropharyngeal membrane
Eventually the neural plate extends beyond the
notochord.
6

Formation of the Neural

Tube
neural plate invaginates along its central axis
to form a longitudinal median neural groove,
neural groove has neural folds on each side

The neural folds become particularly

prominent at the cranial end of the embryo.
neural folds are the first signs of brain development.

Formation of the Neural

Tube
the neural folds move together and
fuse, converting the neural plate into
a neural tube.
neural tube is the primordium of the
CNS.

Formation of the Neural

Tube
Neural tube soon separates from surface
ectoderm
Neural crest cells undergo an epithelial to
mesenchymal transition and migrate
away
Free edges of surface ectoderm fuse and
becomes continuous over neural tube.

Formation of the Neural

Tube
Subsequently, the surface ectoderm
differentiates into the epidermis.
Neurulation is completed during the
fourth week.

10

Neural Crest Formation

some neuroectodermal cells lying along
inner margin of each neural fold lose their
epithelial attachments.
neural crest cells form neural crest
between neural tube and overlying surface
ectoderm
neural crest is a flattened irregular mass
11

Neural Crest Formation

The neural crest separates into right and
left parts
And shift to the dorsolateral aspects of
the neural tube
There, they give rise to the sensory
ganglia of the spinal and cranial nerves.
12

Neural Crest Formation

Neural crest cells move both into and
over surface of somites.
neural crest cells disseminate widely
but usually along predefined
pathways.

13

Neural crest cells give rise to:

spinal ganglia (dorsal root ganglia)
ganglia of autonomic nervous system
neurolemma sheaths of peripheral nerves
ganglia of cranial nerves V, VII, IX and X

(contribute to)
leptomeninges (contribute to)
pigment cells (contribute to)
suprarenal medulla

connective tissue components in head

14

Development of the Brain

develops from neural tube cranial to
the fourth pair of somites.

15

Primary Brain Vesicles

brain develops from it
Formed by fusion of neural folds in the cranial
region and closure of the rostral neuropore
Primary brain vesicles includes:
forebrain (prosencephalon)
midbrain (mesencephalon)
hindbrain (rhombencephalon)
16

17

Secondary Brain Vesicles

there are five secondary brain vesicles.
forebrain divides into two:
telencephalon
Diencephalon

midbrain does not divide

hindbrain partly divides into:
metencephalon
myelencephalon

18

Brain Flexures
Midbrain and cervical Flexures

Produced by the rapid growth and

ventral bending of embryonic brain
with head fold.
Midbrain flexture in midbrain region
cervical flexure at junction of
hindbrain and spinal cord.
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Brain Flexures
Pontine Flexure

Produced by unequal growth of the

brain between midbrain and cervical
flexures.
It is in the opposite direction of the
above flexures.
It results in thinning of the roof of
21

Brain flexure results in:

variation in the outline of transverse
sections at different levels of the brain
from spinal cord.
variation in the position of the gray and
white matter.

22

Difference from spinal cord development

The sulcus limitans extends cranially to
the junction of the midbrain and forebrain.
The alar and basal plates are recognizable
only in the midbrain and hindbrain.

23

Hindbrain
cervical flexure demarcates it from the
spinal cord.
Later, this junction is defined as level of
superior rootlet of first cervical nerve
The pontine flexure divides the hindbrain
into caudal (myelencephalon) and rostral
(metencephalon) parts.
24

Hindbrain
myelencephalon becomes medulla
oblongata
metencephalon becomes pons and
cerebellum.
cavity of hindbrain becomes 4th
ventricle and central canal in
25

Myelencephalon
Caudal part
Resembles the spinal cord, both
developmentally and structurally.
Neural canal forms the central canal of
myelencephalon.
Neuroblasts from alar plates migrate into
marginal zone and form gracile nuclei
medially and cuneate nuclei laterally.
26

Myelencephalon
Caudal part
The pyramids:
a pair of fiber bundles on ventral area
of medulla
consist of corticospinal fibers
descending from developing cerebral
cortex.
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Myelencephalon
The rostral part
Wide and rather flat
Pontine flexure causes lateral walls of medulla
to move laterally like pages of an open book.
Its roof plate is stretched and greatly thinned.
cavity of this part of myelencephalon becomes
somewhat rhomboidal (diamond shaped).
alar plates come to lie lateral to basal plates.
motor nuclei generally develop medial to the sensory

nuclei

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Myelencephalon
Neuroblasts in the basal plates

develop into motor neurons.

neuroblasts form nuclei and organize
into three cell columns on each side.

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Myelencephalon
Neuroblasts in the basal plates
The three cell columns from medial to
lateral:
1. general somatic efferent
represented by neurons of the hypoglossal nerve

2. special visceral efferent

represented by neurons innervating muscles
derived from pharyngeal arches

3. general visceral efferent

represented by some neurons of vagus and
glossopharyngeal nerves
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Myelencephalon
Neuroblasts in the alar plates

form neurons arranged in four columns on

each side.

The four nuclei of the alar plate medial to

lateral are:
1. The general visceral afferent
Receives impulses from the viscera

2. The special visceral afferent

Receives taste fibers
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Myelencephalon
Neuroblasts in the basal plates
The four nuclei of the alar plate medial to
lateral are:
3. The general somatic afferent
receives impulses from the surface of the head
4. The special somatic afferent
receives impulses from the ear
Some neuroblasts from alar plates migrate ventrally

and form neurons in olivary nuclei

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Metencephalon

The walls form the pons and cerebellum

the cavity forms the superior part of the fourth
ventricle.
Pontine flexure causes divergence of lateral walls of
pons:
spreads the gray matter in the floor of the fourth ventricle

Neuroblasts in basal plate develop into motor

nuclei and organize into three columns on each
side.

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35

Metencephalon
Cerebellum
develops from thickenings of dorsal parts of the
alar plates.
Initially, the cerebellar swellings project into the
fourth ventricle.
As the swellings enlarge and fuse in the median
plane, they overgrow the rostral half of the fourth
ventricle and overlap the pons and medulla.

36

Metencephalon
Cerebellum
Neuroblasts from alar plates differentiates into
neurons of the cerebellar cortex:
central nuclei, largest of which is dentate
nucleus.
pontine nuclei
the cochlear
vestibular nuclei,
sensory nuclei of the trigeminal nerve.
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The Midbrain
(Mesencephalon)

The neural canal narrows and becomes the cerebral

aqueduct
Neuroblasts of the alar plates:
migrate into the tectum (roof) and aggregate to form
four groups of neurons.
Paired superior colliculiconcerned with visual reflex
Paired inferior colliculiconcerned with auditory
reflex

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The Midbrain
Neuroblasts of basal plates

Migrate into tegmentum of midbrain

And give rise to:
red nuclei
nuclei of 3rd and 4th cranial nerves (CNs),
reticular nuclei
substantia nigra
but some authorities believe that it is
derived from cells in the alar plate that
migrate ventrally
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The Midbrain
Neuroblasts of basal plates

Fibers growing from the cerebrum

form the stemlike cerebral
peduncles anteriorly
The cerebral peduncles become more
prominent as more descending fiber
groups pass through the developing
midbrain on their way to the
brainstem and spinal cord.
40

Forebrain

As closure of rostral neuropore occurs, two

lateral outgrowths appear on each side of
forebrain.
optic vesicles
Is the primordia of retinae and optic nerves.

telencephalic vesicles
arise more dorsally and rostrally.
Is the primordia of the cerebral hemispheres
and their cavities become the lateral

41

Forebrain
Telencephalon
The rostral/anterior part
forebrain including the primordia of the cerebral

hemispheres
Diencephalon:
the caudal /posterior part of the forebrain
Cavities of telencephalon and diencephalon form third

ventricle cavity of diencephalon contributes more.

42

Forebrain
Diencephalon
Three swellings develop in the lateral

walls of the third ventricle, which

later become:
Thalamus
Hypothalamus
Epithalamus
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Forebrain
Diencephalon
The thalamus is separated from:
epithalamus by the epithalamic sulcus
hypothalamus by the hypothalamic sulcus.
hypothalamic sulcus is not a continuation of the
sulcus limitans and does not divide sensory and
motor areas.

46

Diencephalon
Thalamus
develops rapidly on each side and
bulges into the cavity of the third
ventricle, reducing it to a narrow cleft.
Inter-thalamic adhesion
A bridge of gray matter across the third
ventricle formed by the meeting and
fusion of the thalami (in 70% of cases).
47

Diencephalon
Hypothalamus
arises by proliferation of neuroblasts in the

intermediate zone of the diencephalic walls,

ventral to the hypothalamic sulci.
Later, a number of nuclei concerned with

endocrine activities and homeostasis develop.

The mammillary bodies:
pea-sized swellings on ventral surface of the

hypothalamus formed by a pair of pea-sized nuclei

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Diencephalon
Epithalamus

develops from the roof and dorsal

portion of the lateral wall of the
diencephalon.

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The telencephalon
Consists of:
A median part
Its cavity forms the extreme anterior part of

the third ventricle

Two lateral diverticula (cerebral

vesicles)
The primordia of the cerebral hemispheres.
50

 Initially, this medial wall lies in the roof of

the hemisphere and is continuous with
roof of the 3rd ventricle.

51

 Expansion of cerebral hemispheres results in:

They cover diencephalon, midbrain, and
hindbrain, successively.
flattening of the medial surfaces of the
hemispheres.

Cerebral falx:
Formed by the mesenchyme trapped in the
longitudinal fissure between the hemisphere.
52

 How does the cerebral hemispheres

become C shaped?
Because of the outgrowth of cortical
walls than floor due to the presence of
the corpus striatum in the floor.

53

 How does the shape of the lateral

ventricles become C-shaped?
due to the growth and curvature of the
hemispheres.

54

 Caudal end of each cerebral

hemisphere turns ventrally and then
rostrally forming:
the temporal lobe
temporal horn of lateral ventricle
Choroid fissure within it
55

 As the cerebral cortex differentiates, fibers

passing to and from it pass through corpus
striatum and divide it into caudate and
lentiform nuclei.
This fiber pathway-internal capsule
becomes C shaped as hemisphere assumes
this form.
56

 The caudate nucleus becomes

elongated and C shaped, conforming
to the outline of the lateral ventricle.

57

Cerebral Commissures
Groups of nerve fibers connecting
corresponding areas of the cerebral
hemispheres with one another.
They form as the cerebral cortex
develops.

58

Cerebral Commissures
Corpus callosum
The largest cerebral commissure
Initially lies in the lamina terminalis, but gradually
extends beyond the lamina terminalis
Due to addition of fibers as the cortex enlarges

At birth, it extends over the roof of the

diencephalon.

The rest of the lamina terminalis becomes

stretched to form the thin septum pellucidum
59

 Zones of neural tube on the walls of

developing cerebral hemispheres:
Intermediate zone
Cells of this zone migrate into marginal zone
and give rise to cortical layers
gray matter is thus located peripherally
And axons pass centrally to form white matterthe medullary center
60

 Zones of neural tube on the walls of

developing cerebral hemispheres:
Marginal
Ventricular
Subventricular
develops later of all.

61

Sulci and Gyri

Initially, the surface of the cerebral
hemispheres is smooth, later sulci
and gyri develop.
The gyri are caused by infolding of
cerebral cortex.
They increase the surface area of the
cerebral cortex without requiring
increase in cranial size
62

 How does the insula is (L. island)

forms?
Due to the cortex covering the external
surface of the corpus striatum grows
relatively slowly and is soon overgrown.

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Development of the Spinal Cord

Develops from the neural tube
caudal to the fourth pair of
somites.
The lateral walls of the neural
tube thicken, reducing the size
of the neural canalcentral
canal.
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 Initially, wall of the neural tube is

composed of pseudo-stratified, columnar
neuroepithelium.
These cells constitute ventricular zone
which gives rise to all neurons and
macroglial cells.

68

 Marginal zone
Composed of outer parts of the
neuroepithelial cells.
Becomes white matter as axons grow
into it from nerve cell bodies in spinal
cord, spinal ganglia and brain.

69

 Intermediate zone
It is between the ventricular and marginal
zones.
Formed by neuroblasts differentiated from
neuroepithelial cells in ventricular zone.
Neuroblasts become neurons as they
develop cytoplasmic processes
70

Glioblasts (Spongioblasts)
The primordial supporting cells of CNS
Differentiate from neuroepithelial cells, after
neuroblast formation has ceased.
They migrate from ventricular into intermediate
and marginal zones.
they become astroblasts & oligodendroblasts
later astrocytes and oligodendrocytes,
respectively.

71

Ependymal Cells
Produced from neuroepithelial cells when
they cease producing neuroblasts and
glioblasts
They form the ependyma (ependymal
epithelium) lining the central canal of
spinal cord.

72

Microglial Cells (Microglia)

Small cells that are scattered throughout
gray and white matter.
Originate in the bone marrow.
They are part of the mononuclear phagocytic
cell population.
They invade CNS late in the fetal period after
it has been penetrated by blood vessels.
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Sulcus Limitans
a shallow longitudinal groove on
each side
Formed by differential thickening of
the lateral walls.
It separates the alar plate from the
basal plate.
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Alar and Basal Plates

The alar and basal plates produce
longitudinal bulges extending through the
length.
This has functional importance; because of:
Alar plate is associated with afferent function
while the basal with efferent.

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 Cell bodies in the alar plates:

In transverse sections of the corddorsal gray horns
Neuronsafferent nuclei
groups of these nuclei form the dorsal gray columns.

As alar plates enlarge, dorsal median septum

forms.

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 Cell bodies in the basal plates:

form the ventral and lateral gray columns.
In transverse sectionsventral and lateral gray
horns.

Ventral roots of the spinal nerves:

Develop when axons of ventral horn cells grow
out of the spinal cord.

Ventral median septum and ventral median

fissure
Form as the basal plates enlarge, on each side of
the median plane, ventrally.
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Development of the Spinal Ganglia

Dorsal Root Ganglia

Unipolar neurons in the spinal ganglia.

Derived from neural crest cells
axons of cells in spinal ganglia are at first
bipolar, but two processes unite in a Tshaped fashion.

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Peripheral Process
Axons structurally
dendrite functionally
pass in spinal nerves to sensory endings
in somatic or visceral structures

80

Central Processes
Axons both structurally and functionally
enter the spinal cord and constitute the
dorsal roots of spinal nerves.

81

Development of the Spinal

Meninges
Develops by the condensation of
mesenchyme surrounding the neural tube.
Dura mater:
Formed by the thickening of external layer of

this membrane

Leptomeninges
composed of pia mater and arachnoid mater
derived from neural crest cells.
82

 Fluid-filled spaces appear within

leptomeninges and coalesce to form
subarachnoid space.
Origin of pia mater and arachnoid from a
single layer is indicated in adult by
arachnoid trabeculae

83

Positional Changes of the Spinal

Cord
The spinal cord in the embryo extends the
entire length of the vertebral canal.
In adults spinal cord extends only up to the
inferior border of the first lumbar vertebra
The spinal nerves pass through the
intervertebral foramina opposite their levels
of origin.
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 Why does the position of the spinal

cord becomes higher with age?
Because the vertebral column and dura
mater grow more rapidly than the spinal
cord.

86

 Spinal nerve roots, especially those of the

lumbar and sacral segments, run obliquely
from the spinal cord to the corresponding level
of the vertebral column in adult.
But in embryo it is in the corresponding level.
How does these difference has occurred?
This is due to positional change of spinal cord with
age
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 medullary cone (conus medullaris)

The nerve roots inferior to the end of the
cord
form cauda equinaa bundle of spinal
nerve roots

Dura mater and arachnoid mater end

at S2 vertebra in adults
Pia mater extends throughout length
of vertebral column.
88

 Terminal filum (L. filum terminale):

Pia mater distal to caudal end of the spinal cord
extends from the medullary cone and attaches
to the periosteum of the first coccygeal
vertebra.
indicates the original level of the caudal end of
the embryonic spinal cord

89

Nervous System Malformations

Malformations of the Spinal Cord

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