DEVELOPMENT OF CNS

INTRODUCTION

The first indications of the developing nervous system

appear during the third week as the neural plate and
neural groove develop on the posterior aspect of the
trilaminar embryo
It is the notochord and paraxial mesenchyme that induce
the overlying ectoderm to differentiate into the neural
plate.
 Neurulation
Formation of the neural plate and neural tube— begins
during the fourth week (22– 23 days) in the region of the
fourth to sixth pairs of somites.
At this stage, the cranial two-thirds of the neural plate
and tube, as far caudal as the fourth pair of somites,
represent the future brain, and the caudal one third of
the plate and tube represents the future spinal cord.
 Neurulation
Fusion of the neural folds and formation of the neural
tube begins at the fifth somite and proceeds in both
cranial and caudal directions until only small areas of the
tube remain open at both ends.
The neural tube lumen becomes the neural canal, which
communicates freely with the amniotic cavity.
The cranial opening, the rostral neuropore, closes at
approximately the 25th day and the caudal neuropore
closes at approximately the 27th day
 Derivatives of neural tube
It gives rise to the CNS:
The cranial part becomes the brain
The caudal part becomes the spinal cord
The cavity gives rise to the central canal of the spinal
cord and ventricles of the brain
 Derivatives of Neural crest
Pseudounipolar ganglion cells of the spinal and cranial
nerve ganglia
Schwann cells (neurolemmal sheath cells that form
myelin in the PNS)
Multipolar ganglion cells of the autonomic ganglia
Leptomeninges (pia and arachnoid cells)
Chromaffin cells of the suprarenal medulla
Pigment cells (melanocytes)
Odontoblasts (dentin-forming cells), dental papilla,
and the dental follicle
Aorticopulmonary septum of the heart
 Parafollicular cells (calcitonin-producing C-cells)
Skeletal and connective components of the
pharyngeal arches
 Stages of Neural Tube Development
A. Vesicle development
The three primary brain vesicles and associated flexures
Develop during the fourth week
Give rise to dilations of the primary brain vesicles
and two curvatures.
 Brain vesicles
Prosencephalon (forebrain)
Associated with the appearance of the optic vesicles.
gives rise to:
Telencephalon (endbrain)
Diencephalon (between-brain)
Mesencephalon (midbrain)
• Remains as the mesencephalon
Rhombencephalon (hindbrain)
Gives rise to:
o Metencephalon (after brain); forms the pons and
cerebellum
oMyelencephalon (medulla oblongata)
 Flexures
Cephalic flexure (midbrain flexure)
Located between the prosencephalon and the
rhombencephalon
 Cervical flexure
Located between the rhombencephalon and the future spinal
cord
Diagrammatic sketches of the brain vesicles indicating the adult derivatives
of their walls and cavities.
 Secondary Brain Vesicles
There are five secondary brain vesicles (with four ventricles) and
they become visible in the sixth week
The brain vesicles are visible as the primordia of the five major brain
divisions.
Telencephalon:
Has lateral outpocketings that form the cerebral hemispheres.
Has ventral outpocketings that form the olfactory bulbs.
Has visible lateral ventricles.
Diencephalon:
The third ventricle
Optic chiasm and optic nerves
Infundibulum
Mammillary eminences become visible
Mesencephalon:
Contains a large cavity that will become the cerebral
aqueduct
Metencephalon
Separated from the mesencephalon by the rhombencephalic
isthmus.
Separated from the myelencephalon by the pontine flexure.
Contains rhombic lips on the dorsal surface, which give rise
to the cerebellum
Becomes the pons and the cerebellum
Contains the rostral half of the fourth ventricle
Myelencephalon (medulla oblongata)
Lies between the pontine and cervical flexures
Becomes the medulla
Contains the caudal half of the fourth ventricle
 Histogenesis
• Cells of the neural tube wall are neuroepithelial cells that
give rise to:
a. Neuroblasts
Form all neurons found in the CNS
b. Glioblasts (spongioblasts) :
For the most part form after cessation of neuroblast
formation (except for radial glial cells, which develop before
neurogenesis is complete).
 Form the supporting cells of the CNS
1. Macroglia
Astroglia (astrocytes)
• Contain glial fibrillary acidic protein (GFAP), a marker for
astroblasts.
• Surround blood capillaries with their perivascular feet.
Radial glial cells
• are of astrocytic lineage and are GFAP-positive. Provide
guidance for migrating neuroblasts
• Oligodendroglia (oligodendrocytes), produce the
myelin of the CNS.
• Ependymal cells: are ciliated
A. Ependymocytes: line the ventricles and the central
canal.
B. Tanycytes : are located in the wall of the third
ventricle.
Transport substances from the cerebrospinal fluid (CSF) to the
hypophyseal portal system
C. Choroid plexus cells: produce CSF
Bound together by tight junctions (zonulae occludentes) that
represent the blood–CSF barrier.
Microglia (gitter cells):
The scavenger cells of the CNS
Arise from monocytes, not from glioblasts
Invade the developing nervous system in the third week with
the developing blood vessels
Are formed within the wall of the primitive
neural tube. Layers of the neural tube wall
•It has
a. Neuroepithelial (ventricular) layer
 the innermost layer.
 a monocellular layer of ependymal cells
that lines the central canal and future brain
ventricles.
b. Mantle (intermediate) layer:
 The middle layer.
 Consists of neurons and glial cells, the
central gray matter of the spinal cord.
 The contains the developing alar and basal
plates.
c. Marginal layer
 the outermost layer. • contains nerve fibers
of neuroblasts of the mantle layer and glial
cells.
 produces the white matter of the spinal
cord through the myelination of axons
growing into this layer.
• Histogenesis of cells in the central
nervous system.

• After further development, the

multipolar neuroblast (lower left)
becomes a nerve cell or neuron.

• Neuroepithelial cells give rise to

all neurons and macroglial cells.

• Microglial cells are derived from

mesenchymal cells that invade the
developing nervous system with
the blood vessels.
 Development of the Spinal Cord
The spinal cord develops from the caudal part of the
neural plate and the caudal eminence.
The neural tube caudal to the fourth pair of somites
develops into the spinal cord.
The lateral walls of the neural tube thicken, gradually
reducing the size of the neural canal until only a minute
central canal of the spinal cord is present at 9 to 10
weeks.
Initially, the wall of the neural tube is composed of a
thick, pseudostratified, columnar neuroepithelium
 Histogenesis
These neuroepithelial cells constitute the ventricular zone
(ependymal layer), which gives rise to all neurons and
macroglial cells (macroglia) in the spinal cord.
Macroglial cells are the larger members of the neuroglial
family of cells, which includes astrocytes and
oligodendrocytes.
Soon a marginal zone composed of the outer parts of the
neuroepithelial cells becomes recognizable.
This zone gradually becomes the white matter of the
spinal cord as axons grow into it from nerve cell bodies
in the spinal cord, spinal ganglia, and brain.
Some dividing neuroepithelial cells in the ventricular
zone differentiate into primordial neurons— neuroblasts.
These embryonic cells form an intermediate zone
(mantle layer) between the ventricular and marginal
zones. Neuroblasts become neurons as they develop
cytoplasmic processes.
The supporting cells of the CNS—glioblasts
(spongioblasts)— differentiate from neuroepithelial cells,
mainly after neuroblast formation has ceased.
The glioblasts migrate from the ventricular zone into the
intermediate and marginal zones.
Some glioblasts become astroblasts and later astrocytes,
whereas others become oligodendroblasts and eventually
oligodendrocytes.
When the neuroepithelial cells cease producing
neuroblasts and glioblasts, they differentiate into
ependymal cells, which form the ependyma (ependymal
epithelium) lining the central canal of the spinal cord.
Microglia (microglial cells), which are scattered
throughout the gray and white matter, are small cells that
are derived from mesenchymal cells.
Microglia invade the CNS rather late in the fetal period
after it has been penetrated by blood vessels.
Microglia originate in the bone marrow and are part of
the mononuclear phagocytic cell population.
 Fundamental Cross-Sectional Organization of the
Developing Neural Tube
The developing spinal cord is a useful prototype for
studying the overall structural and functional features of
the central nervous system because
it preserves its fundamental organization through
much of development.
With the beginning of cellular differentiation in the
neural tube, the neuroepithelium thickens and appears
layered.
The layer of cells closest to the lumen (central canal)
of the neural tube remains epithelial and is called the
ventricular zone (the ependymal zone in older
literature).
 Spinal cord
This zone, which still contains mitotic cells, ultimately
becomes the ependyma, a columnar epithelium that
lines the ventricular system and central canal of the
central nervous system.
Farther from the ventricular zone is the intermediate
(formerly called mantle) zone, which contains the cell
bodies of the differentiating postmitotic neuroblasts.
As the neuroblasts continue to produce axonal and
dendritic processes, the processes form a peripheral
marginal zone that contains neuronal processes, but not
neuronal cell bodies.
As the spinal cord matures, the intermediate zone
becomes the gray matter, in which the cell bodies of the
neurons are located.
The marginal zone is called the white matter because
of the color imparted by the numerous tracts of
myelinated nerve fibers in that layer.
When the basic layers in the spinal cord. are established,
several important topographical features can be
recognized in cross sections of the spinal cord.
A sulcus limitans within the central canal divides the
spinal cord into a dorsal alar plate and a ventral basal
plate on each side of the central canal.
The right and left alar plates are connected dorsally over
the central canal by a thin roof plate, and the two basal
plates are connected ventrally by a floor plate.
The basal plate represents the motor component of the
spinal cord.
Axons arising from neurons located in the ventral horn
of the gray matter exit the spinal cord as ventral motor
roots of the spinal nerves
The gray matter of the alar plate, called the dorsal horn,
is associated with sensory functions.
Sensory axons from the spinal ganglia (neural crest
derivatives) enter the spinal cord as dorsal roots and
synapse with neurons in the dorsal horn.
A small projection of gray matter between the dorsal and
ventral horns at spinal levels T1 to L2 contains cell
bodies of autonomic neurons.
This projection is called the lateral horn or sometimes
the intermediolateral gray column
 Myelination
• It commences in the fourth fetal month in the spinal
cord motor roots.
1. Oligodendrocytes accomplish myelination of the CNS.
2. Schwann cells accomplish myelination of the PNS.
3. Myelination of the corticospinal tracts is not complete
until the end of the second postnatal year (i.e., when
the corticospinal tracts become myelinated and
functional).
4. Myelination of the association neocortex extends into
the third decade
 Positional changes of the spinal cord
Disparate growth results in formation of the cauda
equina, consisting of dorsal and ventral roots (L3– Co)
that descend below the level of the conus medullaris,
and in formation of the non neural filum terminale,
which anchors the spinal cord to the coccyx.
At 8 weeks, the spinal cord extends the entire length of
the vertebral canal.
At birth, the conus medullaris extends to the level of the
third lumbar vertebra (VL3).
 In adults, the conus medullaris terminates at the VL1–
VL2 interspace or intervertebral disc
 Medulla oblongata

1. Closed (caudal) medulla

A. Alar plate
sensory neuroblasts give rise to:
I. Dorsal column nuclei, which consist of the gracile and
cuneate nuclei
II. Inferior olivary nuclei, which are cerebellar relay nuclei
III. Solitary nucleus, which forms the GVA (taste) and special
visceral afferent (SVA) column
IV. Spinal trigeminal nucleus, which forms the GSA column
V. Cochlear and vestibular nuclei
• Form the special somatic afferent (SSA) column.
• Lie in the medullopontine junction.
Basal plate motor neuroblasts give rise to:
i. Hypoglossal nucleus, which forms the GSE column
ii. Nucleus ambiguus, which forms the special visceral efferent
(SVE) column (CN IX, CN X, and CN XI)
iii. Dorsal motor nucleus of the vagal nerve (CN X) and the
inferior salivatory nucleus of the glossopharyngeal nerve
(CN IX), which form the GVE column
2. Open (rostral) medulla
• Extends from the obex to the striae medullares of the
rhomboid fossa
• Formation of the pontine flexure causes the lateral walls
of the rostral medulla to open like a book and form the
rhomboid fossa (the floor of the fourth ventricle)
a. Alar plate
• lies lateral to the sulcus limitans.
• its sensory neuroblasts give rise to:
(i) Solitary nucleus
• forms the GVA and SVA columns.
Brain stem
 Medulla oblongata

(ii) Cochlear and vestibular nuclei

• Form the special SSA column.
(iii) Spinal trigeminal nucleus
• Forms the GSA column.
b. Basal plate
• Lies medial to the sulcus limitans.
its motor neuroblasts give rise to:
Hypoglossal nucleus: forms the GSE column.
Nucleus ambiguus: forms the SVE column.
 Dorsal motor nucleus of the vagal nerve and the inferior
salivatory nucleus of CN IX: form the GVE column.
 Medulla oblongata

Roof plate
 forms the caudal roof of the fourth ventricle.
the tela choroidea, a monolayer of ependymal cells
covered with pia mater.
invaginated by pial vessels to form the choroid
plexus of the fourth ventricle.
 METENCEPHALON (PONS)
Metencephalon develops from the rostral division of the
rhombencephalon.
• Gives rise to the pons and the cerebellum
1. Alar plate sensory neuroblasts give rise to:
A. Solitary nucleus, which forms the GVA and the SVA
(taste) columns of CN VII
B. Cochlear and vestibular nuclei, which form the SSA
column of CN VIII
C. Spinal and principal trigeminal nuclei, which form
the GSA column of CN V
D. Pontine nuclei, which consist of cerebellar relay
nuclei (pontine gray)
2. Basal plate motor neuroblasts give rise to:
A. Abducent nucleus of CN VI, which forms the GSE column
B. Facial and trigeminal motor nuclei of CN VII and CN V,
which form the SVE column
C. Superior salivatory nucleus, which forms the GVE column
of CN VII
3. Base of the pons
Contains pontine nuclei from the alar plate.
Contains corticobulbar, corticospinal, and corticopontine fibers
with cell bodies located in the cerebral cortex.
Contains pontocerebellar fibers, which are axons of neurons
found in the pontine nuclei
 Metencephalon(cerebellum)
Is formed by the rhombic lips, which are the thickened alar
plates of the mantle layer.
The rostral part of the cerebellum is derived from the caudal
mesencephalon.
The cerebellar anlage (primordium) gives rise to:
1. Vermis, by midline growth
2. Cerebellar hemispheres, by lateral growth
3. Three-layered cerebellar cortex (molecular layer, Purkinje
cell layer, and granular [internal] cell layer)
4. four pairs of cerebellar nuclei, by cell migration from the
ventricular zone into the marginal layer
 Metencephalon(cerebellum)
5. External granular layer (EGL)
is a germinal (proliferative) layer on the surface of the
cerebellum
present from week 8 of development to the end of
the second postnatal year.
Persistent cell nests may give rise to a neoplasm
medulloblastoma
is sensitive to antiviral agents, which block the
synthesis of DNA.
6. Folia and fissures, by cortical growth
 Mesencephalon(midbrain)
It develops from the walls of the mesencephalic vesicle.
Contains the cerebral aqueduct, which develops from the
mesencephalic cavity.
 Alar plate sensory neuroblasts
• form the cell layers of the superior colliculi and the nuclei of the
inferior colliculi.
 Basal plate motor neuroblasts give rise to the:
1. Trochlear and oculomotor nuclei of CN IV and III, which form
the GSE column
2. Edinger-Westphal nucleus of CN III, which forms the most
rostral cell group of the GVE column
3. Red nucleus and substantia nigra
Basis pedunculi (crus cerebri)
• contains corticobulbar, corticospinal, and corticopontine fibers,
derived from the cerebral cortex of the telencephalon.
 illustration (transverse section) of the development of the midbrain. The alar plate
gives rise to the layers of the superior colliculus and to the nuclei of the inferior
colliculus. The basal plate gives rise to the oculomotor and trochlear nuclei, the
substantia nigra, and the red nucleus. The cerebral peduncles contain the
descending corticospinal tracts.
 Diencephalon
• Develops from the caudal part of the prosencephalon,
within the walls of the primitive third ventricle.
1. Epithalamus
Develops from the embryonic roof plate
Gives rise to the pineal body (epiphysis) and the habenular
nuclei.
Gives rise to the habenular and posterior commissures.
Gives rise, from the roof plate and the pia mater, to the tela
choroidea and choroid plexus of the third ventricle.
2.Thalamus (dorsal thalamus)
An alar plate derivative that gives rise to thalamic nuclei.
Includes the metathalamus, which includes the lateral
geniculate body (relays visual impulses) and the medial
geniculate body (relays auditory impulses).
3. Hypothalamus
Develops ventral to the hypothalamic sulcus from the alar
plate and floor plate.
Gives rise to hypothalamic nuclei, including the mamillary
bodies, and to the neurohypophysis
4. Subthalamus (ventral thalamus)
An alar plate derivative located ventral to the thalamus and
lateral to the hypothalamus.
Includes the subthalamic nucleus, zona incerta, and lenticular
and thalamic fasciculi (fields of Forel).
Contains subthalamic neuroblasts that migrate into the
telencephalon and form the globus pallidus (pallidum), a basal
ganglion.
Optic vesicles, cups , and stalks
• are derivatives of diencephalic vesicle walls.
• give rise to the retina, optic nerve, optic chiasm, and optic tract.
Hypophysis (pituitary gland)
1. Anterior lobe (adenohypophysis)
Develops from the Rathke pouch, an ectodermal diverticulum
of the primitive oral cavity (stomodeum).
Remnants of the Rathke pouch may give rise to a congenital
cystic tumor, a craniopharyngioma
Includes the pars tuberalis, pars intermedia, and pars distalis.
2. Posterior lobe (neurohypophysis)
• Develops from a ventral evagination of the hypothalamus.
• Includes the median eminence, infundibular stem, and pars
nervosa.
 Telencephalon
A. Cerebral hemispheres
Develop as bilateral evaginations of the lateral walls of the
prosencephalic vesicle.
Contain the cerebral cortex, cerebral white matter, basal
ganglia, and lateral ventricles.
Interconnected by three commissures: the corpus callosum,
anterior commissure, and hippocampal (fornix)
commissure.
Continuous hemispheric growth gives rise to frontal, parietal,
occipital, and temporal lobes, which overlie the insula and
dorsal brainstem.
B. Cerebral cortex (pallium)
Formed by prosencephalic neuroblasts that migrate in waves
from the mantle layer into the marginal layer and give rise to
cortical cell layers.
Classified phylogenetically into:
1. Neocortex (isocortex), a six-layered cortex
Separated from the paleocortex by the rhinal sulcus, a
continuation of the collateral sulcus.
Represents 90% of the cortical mantle.
2. Allocortex a three-layered cortex, including:
a. Paleocortex (olfactory cortex)
b. Archicortex (hippocampal cortex)
C. Corpus striatum
 Appears in the fifth week as a bulging striatal eminence in the
ventral floor of the lateral telencephalic vesicle.
Gives rise to the basal ganglia: the caudate nucleus, putamen,
amygdaloid nucleus, and claustrum.
The globus pallidus neurons, a basal ganglion, originate in the
subthalamus; they migrate into the telencephalic white matter
and become the medial segments of the lentiform nucleus.
Divided into the caudate nucleus and the lentiform nucleus by
corticofugal and corticospinal fibers; these fibers make up the
internal capsule.
D. Commissures
Fiber bundles that interconnect the two cerebral hemispheres.
Cross the midline via the lamina terminalis.
1. Anterior commissure
The first commissure to appear.
Interconnects the olfactory structures and the middle and
inferior temporal gyri
2. Hippocampal commissure (fornical commissure)
The second commissure to appear. • interconnects the two
hippocampi.
3. Corpus callosum
appears between weeks 12 and 22 of development
is the third commissure to appear.
is the largest commissure of the brain and interconnects the
corresponding neocortical areas of the two cerebral
hemispheres.
does not project commissural fibers from the visual cortex
(area 17) or the hand area of the motor or sensory strips (areas
1, 2, 3, and 4).
E Gyri and sulci (fissures)
• In the fourth month, no gyri or sulci are present;
the brain is smooth or lissencephalic.
• At the eighth month, all major gyri and sulci are
present; the brain is convoluted or gyrencephalic