DEVELOPMENT OF

THE NERVOUS
SYSTEM

BY DR ELEKELE IZIBEYA ALEX

MBBS 2016
TABLE OF CONTENT
 OVERVIEW

 FORMATION OF NEURAL TUBE/CREST

CELLS/ECTODERMAL PLACODES

 DEVELOPMENT OF THE SPINAL CORD

 DEVELOPMENT OF THE BRAIN

 CONCLUSION
OVERVIEW
 Study of development of the nervous system
helps to understand its complex organization
and occurrence of various congenital
anomalies.
 Whole of the nervous system is derived from
ectoderm except its blood vessels and some
neuroglial elements.
 The specific cell population of early
ectoderm, which gives rise to entire nervous
system and special sense organs, is termed
neural ectoderm.
CONT’D
 The neural ectoderm later differentiates into
three structures:
 neural tube,
 neural crest cells,
 and ectodermal placodes.

 The neural tube gives rise to the central

nervous system (CNS), the neural crest cells
form nearly entire peripheral nervous system,
and ectodermal placodes contribute to cranial
sensory ganglia, hypophysis, and inner ear.
FORMATION OF NEURAL
TUBE
 In early embryonic disc, at about 16th day of
embryonic life, the ectoderm overlying the
newly formed notochord thickens in midline
forming neural plate.
 Initially the neural plate is flat and slipper
shaped with narrow end toward the primitive
node. The somatic mesoderm develops on
either side of the notochord.
 The margins of neural plate are elevated as
neural folds. As a result center of the
plate sinks, creating neural groove.
 The neural folds gradually move together toward the
midline and finally fuse to form a cylindrical neural
tube that loses its connection with the surface
ectoderm. The process of neural tube formation is
termed neurulation.

 The fusion of neural folds begins in the middle (region

of fourth somite on 20th day of embryonic
development) and it simultaneously proceeds in the
cephalic and caudal directions. The fusion at the
cranial and caudal ends of neural tube is somewhat
delayed, forming small openings called anterior and
posterior neuropores.
 The neural tube and overlying amniotic cavity,
therefore, remain temporarily in open
communication with each other through these
pores. The anterior neuropore closes earlier, in
the middle of the fourth week at 18–20 somite
stage (i.e., on 25th day), and the posterior
neuropore closes later at the end of fourth week
at about 25 somite stage. By the time the neural
tube is completely closed, it is divided into an
enlarged cranial part and an elongated caudal
part, which later on gives rise to brain and
spinal cord, respectively.
FORMATION OF THE NURAL CREST CELLS

 As the neural folds come together and fuse, cells at

the tips of neural folds break away from the
neurectoderm to form the neural crest cells. The
surface ectoderm of one side becomes continuous
with the surface ectoderm of opposite side over the
neural tube.
 Thus cells at the tips of neural folds (neural crest
cells) do not participate in the neural tube
formation. The neural crest cells at first remain in
the midline between the dorsal surface of the neural
tube and the surface ectoderm, and then forms two-
cell clusters dorsolaterally, one on either side of the
neural tube.
 The neural crest cells differentiate to
form cells of
 dorsal root ganglia,
 sensory ganglia of cranial nerves,
 autonomic ganglia,
 adrenal medulla,
 chromaffin tissue,
 melanocytes, and
 Schwann cells
FORMATION OF ECTODERMAL PLACODES

 Prior to the neural tube closure, the neural

fold contains two types of cell populations:
 neural crest cells
 and neuroep ithelial cells.
 During neurulation, the neural crest cells
are detached and neuroepithelial cells get
incorporated into the surface ectoderm.
These areas of neuroepithelium within the
surface ectoderm are termed ectodermal
placodes.
DEVELOPMENT OF THE SPINAL CORD

 The spinal cord develops from caudal elongated part of

the neural tube.
 Histogenesis of Neural Tube
 The neural tube increases in thickness due to repeated
mitosis of its epithelial lining. By the middle of fifth
week of embryonic development, the transverse
section of recently closed neural tube (according to
classical theory) reveals three distinct layers or
zones. From within outward these are
 (a) matrix (ependymal) zone,
 (b) mantle zone, and
 (c) marginal zone (Fig. 22.3).
 Matrix (ependymal) zone is thick and
lines the enclosed cavity (neurocele). Its
numerous cells undergoing mitosis produce
neuroblasts and spongioblasts; the former
develop into neurons and latter into
neuroglial cells.
 The neuroblasts migrate to the adjacent
mantle zone, the future spinal gray matter
and their axons enter the external marginal
zone, the future white matter.
 Some central processes of dorsal root ganglia
ascend in the marginal zone while others
synapse with neurons in the mantle zone.
 Once histogenesis is complete, the remaining
matrix cells differentiate into ependymal cells
lining the central canal.
 Recently, on the basis of
microspectrophotometric, radioautographic,
and electron microscopic observation the
concept of classical theory is changed.
 Now according to current theory wall of
recently closed neural tube consists of only
one cell type—the pluripotent neuroepithelial
cells. These cells extend over the entire
thickness of the wall and form a thick
pseudostratified neuroepithelium.

 This zonal appearance merely reflects

different phases of their proliferative cycle—
the sequence being termed interkinetic
migration.
 As development proceeds, these neuroepithelial cells
give rise to another cell type having round nuclei with
dark staining nucleoli called nerve cells or
neuroblasts. The neuroblasts form a zone that
surrounds the neuroepithelial layer. It is known as
mantle zone.
 Mantle zone
 later forms the gray matter of the spinal cord. The
outermost layer of the spinal cord contains fibers
emerging from neuroblasts in the mantle layer and is
known as the marginal layer. Myelination of nerve
fiber gives this layer a white appearance and is
referred as the white matter of the spinal cord.
Development of Functional Columns

 On cross section, the cavity of neural tube

appears like a vertical slit. Due to formation
of vertical slit, the dorsal and ventral walls of
neural tube remain thin and are called roof
and floor plates, respectively. The lateral
walls of neural tube get thickened. On each
side, the lateral wall of neural tube is
demarcated into dorsal and ventral regions
by an inner longitudinal sulcus called
 sulcus limitans.
 The cells of dorsal region or alar lamina
are functionally afferent/sensory while
those of basal lamina are efferent/motor.
 The axons of cells of basal lamina leave
the cord as ventral roots and join with
peripheral processes of dorsal root ganglia
to form spinal nerves (Fig. 22.4).
 The cells of alar and basal laminae are
arranged into longitudinal columns. Each
lamina reveals two columns.
 The two afferent columns of alar lamina
receive axons from dorsal root ganglia.
 1. General somatic afferent column: It
extends throughout the spinal cord and
receives impulses from superficial
(cutaneous) and deep (proprioceptive)
receptors.
 2. General visceral afferent column: It is
confined to thoracolumbar and sacral
regions only and receives impulses from
viscera and blood vessels
 The two efferent columns of basal lamina give
rise to motor fibers.
 1. General visceral efferent column: It is
confined to thoracolumbar and sacral regions only
and provides preganglionic fibers (synapsing in
ganglia) to viscera, glands, and blood vessels.
 2. General somatic efferent column: It extends
throughout the spinal cord and provides fibers that
innervate skeletal muscles.
 N.B. The four cell columns in the spinal cord
are termed ‘general’ because three additional
‘special’ columns exist in brainstem.
Positional Changes of the Spinal
Cord (Fig. 22.5)

 At week 8 lengths of spinal cord and vertebral

column are equal. The spinal cord extends along
entire length of vertebral canal and the spinal
nerves exit intervertebral foramina at the level of
their origin. Due to differential growth of the cord
and vertebral column, the intervertebral foramina do
not remain at the level of the spinal nerves. In order
to exit from corresponding intervertebral foramina
due to recession of the spinal cord, the spinal nerves
are forced to go down in oblique direction.
 At week 24, the lower end of spinal cord ends
at S1 vertebrae.
 ● At birth, the lower end of spinal cord ends at
the level of L3 vertebra.
 ● In adults, due to further recession of the cord,
the lower end of spinal cord ends at the lower border of
 L1 vertebra.
 N.B. The obliquity of spinal nerves is minimum in
cervical region and maximum in sacral and coccygeal
region.
 ● The nerve roots (viz., lumbar, sacral, and coccygeal)
that descend below the lower end of spinal cord (the
conus medullaris) surround thin thread-like
prolongation of pia mater from tip of conus medullaris
(the filum terminalis) and form cauda equina.
Development of Brain
 The brain develops from enlarged cranial part of the
neural tube. At about end of fourth week, enlarged
cephalic part shows three distinct dilatations called
 primary brain vesicles (Fig. 22.6). Craniocaudally,
these are
 (a) prosencephalon (forebrain),
 (b) mesencephalon
 (midbrain), and
 (c) rhombencephalon (hindbrain).
 Their cavities form ventricular system of adult brain.
 During fifth week both prosencephalon and
rhombencephalon subdivide into two vesicles, thus
producing five secondary brain vesicles.
 The prosencephalon gives a rostral
telencephalon and caudal diencephalon
(interbrain). The telencephalon develops lateral
diverticula by evagination, which enlarge, overgrow
and cover the caudal diencephalon to form cerebral
hemispheres. The diencephalon thus becomes
 hidden in the lower parts of the cerebral
hemispheres and forms
 thalamus,
 hypothalamus,
 epithalamus, etc.
 The mesencephalon gives rise to midbrain. It
does not show much changes in early part of
development except that its cavity gets
progressively narrowed to form cerebral aqueduct.
 The rhombencephalon divides into rostral
metencephalon, which eventually develops into
 pons and cerebellum,
 and caudal myelencephalon, which gives rise to
medulla oblongata.
 The adult derivatives of brain vesicles are
summarized
 in Table 22.1.
Flexures of the Brain
 Primitive brain presents three flexures:
 1. Pontine flexure at the middle of
rhombencephalon.
 2. Cervical flexure at the junction of
rhombencephalon and spinal cord.
 3. Cephalic (mesencephalic) flexure
in the region of midbrain.
 The cephalic and cervical flexures are
concave ventrally, whereas the pontine
flexure exhibits a ventral convexity (Fig.
22.7).
 The cervical flexure makes a 90° bend
between hindbrain and spinal cord, causing
the brain to be oriented almost at 90° to the
spinal cord.
 The brain assumes its configuration as a
result of differential growth of its vesicles and
flexures.
Pontine Flexure
 Hindbrain is folded at its middle so that it forms an acute
angle ventrally. This changes shape of the tube
dramatically.
 The cavity becomes a diamond-shaped space called
fourth ventricle, which is widest at line of folding
(junction of two parts of the hindbrain—pons and medulla
oblongata) and tapers superiorly to narrow canal of the
midbrain, the aqueduct of Sylvius and inferiorly to the
central canal in the lower part of medulla oblongata (Fig.
22.8). The thin roof is pulled out to cover the space
posteriorly, and the line of folding extends far laterally as
roof of the lateral recesses of the fourth ventricle. At tips
of these recesses and inferior
 angle of the ventricle, the thin roof breaks down forming apertures
(lateral foramina of Luschka and median foramen of Magendie)
through which the cavity of neural tube communicates with the
surrounding subarachnoid space.
 N.B. To understand the formation of rhomboid-shaped cavity of
fourth ventricle due to pontine flexure, take a 4-inch-long piece of a
rubber tube, make a vertical slit, and then bend it. This converts linear
slit into a rhomboid-shaped aperture.
 The flattening of the hindbrain, which results from folding, displaces
alar laminae so that they lie lateral to basal laminae (buckling effect).
Thus sensory nuclei, which arise from the alar laminae, are lateral to
motor nuclei, which arise from the basal laminae. For this reason
sensory cranial nerves are attached laterally and motor cranial nerves
medially to brainstem. The part of hindbrain caudal to the pontine
flexure is called myelencephalon (the future medulla oblongata) and
rostral part from which pons and cerebellum develop is called
metencephalon.
 Cervical Flexure
 Cervical flexure is convex dorsally and
appears at the junction of hindbrain and
spinal cord, making a right angled bend
between them.
 Cephalic Flexure
 Cephalic flexure is convex dorsally and
appears at the midbrain level.
 N.B. The closed rostral end of the neural
tube persists as a thin lamina terminalis.
Development of Ventricular System
(Fig. 22.9)
 The cavities of brain vesicles form the ventricular system
of adult brain.
 ● The hindbrain cavity becomes the fourth ventricle.
 ● The narrowed mesencephalic cavity becomes the
cerebral aqueduct (aqueduct of Sylvius).
 ● The diencephalic cavity becomes the third ventricle.
 ● The twin telencephalic cavities become lateral
ventricles.
 Thus, the brain contains four ventricles: two lateral
ventricles, a third ventricle, and a fourth ventricle.
 The two lateral ventricles communicate with the
third ventricle via interventricular foramina (of
Monro).
 The third ventricle communicates with the fourth
ventricle through the cerebral aqueduct. The fourth
ventricle is continuous below with central canal of
the spinal cord, which presents a small dilatation at
inferior end called terminal ventricle.
 Cerebrospinal fluid (CSF) is formed in the
ventricles, mainly in lateral ventricles by choroid
plexuses. The CSF leaves the ventricular system
through apertures in the roof of ventricle (viz.,
foramen of Magendie and foramina of Luschka)
into subarachnoid spaces around the brain and
spinal cord.
Hindbrain
(Rhombencephalon)
 The caudal part of myelencephalon has a central canal
and forms the closed part of medulla oblongata.
Rostrally the central canal expands as the cavity of
the fourth ventricle, and thus the rostral part of
myelencephalon forms the open part of the medulla
oblongata.
 The floor of fourth ventricle is derived from
myelencephalon (medulla) and metencephalon (pons).
On either side of midline, the floor consists of the basal
and alar laminae, which are separated from each other
by a longitudinal sulcus called sulcus limitans. The
basal and alar laminae, similar to that of spinal
cord, contain motor and sensory nuclei, respectively.
 These nuclei are arranged into longitudinal columns.
In spinal cord as discussed earlier, each lamina
contains two columns, somatic and visceral, but in
the brainstem to supply the derivatives of the
branchial arches that develop around this
region, a special branchial column appears
between somatic and visceral columns of each
lamina. In addition, a special somatic column
appears in the most lateral part of the alar lamina to
receiveimpulses of special sensations of hearing and
balance. Thus in brainstem, the basal lamina contains
three columns and alar lamina contains four columns
as under:
 1. Functional column with basal lamina of brainstem
 (a) Somatic efferent
 (b) Special visceral efferent
 (c) General visceral efferent.
 2. Functional columns in the alar lamina of brainstem
 (a) General visceral afferent
 (b) Special visceral afferent
 (c) General somatic afferent
 (d) Special somatic afferent.
 Note: All motor nuclei of the brainstem are derived from
functional columns of its basal plate, and all the sensory
nuclei from the functional columns of the alar plate (Fig.
22.11).
 The stretched roof plate of rhombencephalic
vesicle forms the roof of fourth ventricle. The roof
consists of a single layer of ependymal cells
covered by a vascular mesenchyme—the pia
mater. Pia mater along with covering layer of
ependymal cells forms tela choroidea.
 Owing to active proliferation of vascular
mesenchyme, the tuft of capillaries of blood
vessels invaginates into the ventricular cavity.
These sac-like invaginations consisting of tela
choroidea and tuft of capillaries form choroid
plexus (Fig. 22.12).
 Dorsolateral parts of the alar laminae of
metencephalon extend medially and dorsally to
form rhombic lips. These meet and fuse in the
midline over the roof of the fourth ventricle and
then grow dorsally to form cerebellum.
 The marginal layer of basal plates of
metencephalon expands considerably to serve as
a bridge for nerve fibers connecting cerebral
cortex and cerebellar cortex (cortico-
pontocerebellar pathways). Since this portion of
metencephalon serves as a bridge, it is known as
pons (pons = bridge).
Midbrain
(Mesencephalon)
 Morphologically the midbrain is the most primitive of
the brain vesicles. It generally retains a cylindrical
form and its narrowed cavity forms the cerebral
aqueduct, which is continuous below with the fourth
ventricle and above with the third ventricle.
 ● Anterior to the cerebral aqueduct, the basal
laminae give rise to tegmentum and substantia
nigra. The marginal layer of each basal lamina
enlarges and forms crus cerebri. These crura serve
as pathways for nerve fibers descending from the
cerebral cortex to the lower centers in pons,
medulla, and spinal cord.
 The cells of alar laminae invade the roof
plate to form bilateral longitudinal elevations
separated by a shallow midline groove. With
further development, each elevation is
subdivided by a transverse groove into upper
and lower parts called superior and
inferior colliculi, respectively.
 Thus, four colliculi (also called corpora
quadrigemina develop into the roof plate
dorsal to the aqueduct of Sylvius and form
tectum.
Forebrain
(Prosencephalon)
 1. The diencephalon develops from the median
portion ofthe prosencephalon. Its cavity is called the
third ventricle.
 The primitive diencephalon consists of two thick lateral
walls, a thin roof, and floor plates.
 Each lateral wall presents a sulcus, the hypothalamic
sulcus, which appears to be rostral continuation
of sulcus limitans.
 The hypothalamic sulcus divides lateral wall into
dorsal and ventral regions. The dorsal region develops
into thalamus.
 The ventral region encroaches on the floor plate and
forms hypothalamus.
 A downgrowth from the floor of anterior
hypothalamus, the neurohypophysis, joins an
upgrowth from the stomodeum, the
adenohypophysis, to form hypophysis cerebri
(pituitary gland).
 The epithalamus comprising pineal gland
and habenular nuclei develops posteriorly in
the roof plate.
 The pineal gland grows posteriorly from the
roof plate at its junction with the midbrain, and
lies on the dorsal surface of midbrain between
the two superior colliculi.
 2. The telencephalon consists of a median part
and two lateral diverticula or cerebral vesicles. The
median part forms a small anterior part of the third
ventricle, and the lamina terminalis, which limits the
ventricle rostrally. The lamina terminalis represents
the cephalic end of the primitive neural tube and
corresponds with the site of closure of anterior
neuropore.
 The lateral diverticula or cerebral vesicles represent
rudiments of cerebral hemispheres. The cavities of
hemispheres, the lateral ventricles, communicate
with the cavity of diencephalon, the third ventricle,
through the interventricular foramina.
 The developing cerebral hemisphere enlarges forward,
upward, and backward in that order. As the vesicle grows
backward it overlaps successively diencephalon,
mesencephalon, and cerebellar rudiments. The lowest
parts of medial walls of hemispheres in the region where
they are attached to the roof of diencephalon remain very
thin due to disproportionate growth of various parts of the
hemispheres.
 Through this thin wall, the choroid plexus of third ventricle
protrudes laterally into lateral ventricle along a line known
as choroid fissure. Immediately above the choroid
fissure, the medial wall of the hemisphere thickens to form
hippocampus. With subsequent massive expansion of
the cerebral
 hemispheres (neocortex), the hippocampus is
displaced posteroinferiorly into the lateral
ventricle; the fornix is drawn out as an
efferent tract on its medial aspect. The choroid
fissure also becomes curved, interposed
between the fornix and diencephalon.
 Corpus striatum develops bilaterally in
the floor of telencephalon adjacent to
thalami. Primitively these areas of gray matter
(corpus striatum) are sensory–motor control
centers.
 Subsequent to massive development of
neocortex, a major pathway must develop for
descending fibers from the cerebral cortex
and ascending fibers from the thalamus to the
cerebral cortex; the only possible route is
through this region. Hence, these fibers that
form internal capsule on each side divide
the corpus striatum into two parts: (a) a
dorsomedial portion, the caudate
 nucleus, and (b) a ventrolateral portion,
the lentiform nucleus (Fig. 22.13A, B).
 N.B. The cerebral hemisphere starts growing/expanding in
the region of interventricular foramen. It grows rapidly forward
(formingfrontal lobe), dorsally (forming parietal lobe), posteriorly
(forming occipital lobe), and then anteroinferiorly (forming
temporal lobe).
 This curved pattern of expansion of cerebral hemisphere from
interventricular foramen around the diencephalon causes
structures related to it (viz., lateral ventricle, corpus callosum,
fornix, choroid fissure, and caudate nucleus) to acquire C-shaped
forms.
 The three meninges/membranes (i.e., pia mater, arachnoid
mater, and dura mater) surrounding the brain and spinal cord are
derived from mesenchyme surrounding the neural tube.
 However, according to some workers, the pia mater and the
arachnoid mater (leptomeninges) are derived from neural crest
and do not from mesenchyme.
REFERENCE
 TEXT BOOK OF EMBRYOLOGY BY
VIRSHRAM SINGH