Central Nervous System

Development
 Objectives
1. To describe how the human nervous system
develops.
2. To outline the origin of the cells of the nervous
system.
3. To discuss the embryological basis of the
congenital malformations of the central nervous
system.
 Bonus point:
1. To review applications of Central Nervous
System development.
Development of the Central
Nervous System
 The central nervous system develops from
the neural tube.
neurulation

 Commences after gastrulation (3rd week).

 It is the formation of the neural tube.
 First indication of the developing nervous
system is the formation of the neural plate.
 The folding commences in the cervical region
of the embryo and proceeds cranio-caudally
( i.e. Cranially and caudally).{level of the 5th
cervical somite}.
 The neural plate folds under influence of
the notochord to form the neural tube.
Neurulation continued

 Through the process of neurulation the neural

plate forms the neural tube.
 The stages of neural tube and neural plate
occur in different regions of the body: in one
region of the body the neural ectoderm is at
neural tube stage and in the other region it is
at neural plate stage.
 Neuromeres are segments of the neural tube
more apparent in the body wall regions than
the head.
Result of neurulation
 Formation of the neural tube and brain vesicles.
 NB: it is not all of the neuro-ectoderm that is
incorporated into the neural tube some of it is
detached and forms the neural crest.
 The neural crest migrates in 3 directions
1. Ventral steam: autonomic ganglia (pre-vertebral,
para-vertebral & enteric)
2. Dorsal stream : joins dermo-my0tomal pert of
somite to form melanocytes and DRG.
3. Cranial stream: forms ecto-mesenchyme that
contributes to musculoskeletal structures of the
head and neck
Vesicle formation

 Initially the neural tube is open @ its cranial and

caudal end via the anterior/superior neuropore
and caudal/inferior neuropore.
 The neuropores close Cranial(day 24) caudal(day
27).
 At the cranial end dilations arise forming the 3
primary brain vesicles:
 Prosencephalon
 Mesecencephalon
 Rhomboencephalon
Spinal cord
 The spinal cord is formed after closure of the
neuropores.
 Initially it is co-extensive with the vertebral
column but due to differential growth rates the
vertebral column outgrows it.
 The interior of the spinal canal is lined with neuro-
epithelium consisting of neuroblasts.
 The neural cells migrate out of the neuroepithelium
and form the cells of the adult nervous system
 NB: ALL THE CELLS OF THE CENTRAL NERVOUS
SYSTEM ARISE FROM THE NEUROEPITHELIUM
EXCEPT MICROGLIA.
Basal and alar plates

 Neuroblasts migrate out of the neuro-

epithelium and surround the neural canal.
 Those that are situated ventrally form the
basal plates (anterior horn cells[motor]).
 Those that are posterior form the alar
plates( dorsal horn cells[sensory]).
 Those that remain as part of the neuro-
epithelium form the ependymal layer.
Development of the Spinal Cord
Neural Tube Histogenesis
Development of the Medulla
Development of the medulla

 The most important feature that occurs at the spino-

medullary junction is ALAR PLATE EVERSION.
 This occurs due to the presence of a thin roof plate
by virtue of expansion of the central canal to form
the IVth ventricle.
 Thus the alar plates come to lie lateral to the basal
plates.
 This explains why the sensory nuclei of the cranial
nerves are lateral to the motor nuclei.
 I.E: SENSORY NUCLEI ARE EITHER DORSAL OR
LATERAL WITH MOTOR NUCLEI BEING MEDIAL.
Cranial Nerve Components -
Cell Columns

Show Efferent Cell Columns

 Spinal nerves contain 4 functional fiber types: general somatic
afferents (GSA), general visceral afferents (GVA), general
somatic efferents (GSE) and general visceral efferents (GVE).
 In cranial nerves there are 3 additional functional components;
special somatic afferents (SSA), special visceral (branchial)
efferents (SVE) and special visceral (branchial) afferent (SVA).
 Cranial nerves may contain anywhere from 1 to 5 fiber types.
 Hence, representatives of their cell columns will only be present
at those levels of the brain where there is a cranial nerve that
requires them i.e., many cell columns will be discontinuous.
 In the spinal cord, the components are represented by columns of
cells, extending longitudinally, that are more or less continuous.
 The basal plate gives rise to the GSEs and GVEs in the ventral
gray horn.
 The GSE cell column is a continuous cell column (supplying
skeletal muscle of somite origin) throughout the cord.
 The GVE cell column is an interrupted one - it is represented by
the intermediolateral cell column from a) C8 - L2 and b) S2 - S4.
 The alar plate gives rise to the:
 a) continuous GSA cell column represented in the dorsal gray
by nucleus posteromarginalis, substantia gelatinosa, and
nucleus proprius,
 b) nucleus dorsalis (of Clarke) found between C8 - L3 at the
base of the dorsal gray horn, and
 c) nucleus gracilis and cuneatus which is present in the low
medulla but which receives discriminative touch and
proprioception from spinal cord levels.
 Sensory fibers from the viscera enter the cord and synapse on
the GVA cell column at the base of the dorsal gray horn
between C8 - L2 and S2 - S4.
 The brainstem develops similarly to the cord i.e., basal and alar
plates, but as the roof of the 4th ventricle thins and the medulla
and pons “open up”, alar plate derivatives come to lie laterally to
those of the basal plate.
 Also, the addition of special sensory and special motor
components introduce certain changes from the plan of the cord.
 None-the-less, the concept of cell columns of specific neuronal
components, continuous from the cord and extending into the
brain stem, is a useful one.
 The concept allows for the anticipation of the location of even
discontinuous cell columns; functional cell columns will appear
in approximately the same dorsal-ventral or medial-lateral
positions in whatever level of the brainstem they appear.
 This concept provides a logical scheme to the CNS in spite of
what at first appears to be random.
 1 - The continuous GSA cell column of the spinal cord
dorsal gray horn which handles pain, temperature and
touch sensations is continued without interruption into the
medulla, pons and midbrain.
 In these locations it is variably known as the spinal nucleus
of V, principal sensory nucleus of (of CN V) and the
mesencephalic nucleus (of CN V).
 Any CN carrying GSA information will terminate in these
trigeminal nuclei, derived from the alar plate.
 Proprioceptive GSA information destined for the
cerebellum from the lower extremity terminate in the
nucleus dorsalis of the cord.
 Similar proprioceptive information from the upper
extremity passes to the analagous rostral representation
called the accessory cuneate nucleus in the low medulla.
 2 - The discontinuous GVA cell column of the spinal cord dorsal gray
horn is recognized throughout the medulla when it resumes as the
nucleus of the tractus solitarius. Any CN carrying GVA information will
terminate in this cell column.
 3 - The continuous GSE cell column of the spinal cord ventral gray horn
is represented throughout the brainstem by an interrupted cell column
of neurons supplying skeletal muscle of head somite origin.
 In the medulla there is the motor nucleus of CN XII, in the pons there is
the motor nucleus of CN VI, in the midbrain it is represented by the the
nearly continuous cell column of CNs III and IV.
 4 - The discontinuous GVE cell column of the spinal cord ventral gray
horn resumes in the medulla as the dorsal motor nucleus of the vagus
and the slightly more rostral inferior salivatory nucleus (of CN IX).
 In the caudal pons this discontinuous cell column is represented by the
superior salivatory nucleus (of CN VII).
 In the midbrain, this interrupted cell column appears again as the
nucleus of Edinger-Westphal (of CN III) at the level of the superior
colliculus.
 5 - Special visceral (branchial) afferents (SVA) are fibers from taste buds
and are carried by CNs VII, IX and X.
 Upon entering the brainstem, they travel with the GVAs, in the tractus
solitarius to the most rostral end of its nucleus (in the pons) where it is
called the gustatory portion of the solitary nucleus.
 6 - Special visceral (branchial) efferents (SVE) are represented in the
brainstem by an interrupted cell column that has no equivalent in the
cord.
 These neurons innervate skeletal muscle that developed from the
mesoderm of the branchial arches e.g., larynx, pharynx, facial muscles,
muscles of mastication.
 In the medulla it is represented by nucleus ambiguus (CN IX and X) while
in the pons it is represented by the motor nuclei of CN VII and V.
 7 - Special somatic afferents (SSA) are found only in supraspinal
locations and are represented by the laterally-lying vestibular and
auditory nuclei in the medulla and pons. They develop from branchial
arch structures.
 Cranial nerves I and II serve vision (SSA) and olfaction (SVA). However,
these are not true nerves. Rather they develop as evaginations of the
telencephalon (olfactory nerve) and the diencephalon (optic nerve).
Cranial Nerve Components -
Cell Columns

Show Efferent Cell Columns

Development of the Medulla
Development of the Pons
 The metencephalon is the more rostral component of the hindbrain and
develops into 2 parts, the pons and cerebellum.
 The pons consists of 2 parts: a) the phylogenetically older dorsal portion
called the pontine tegmentum which lies in the floor of the 4th ventricle
and is continuous with the medulla and exhibits a similar organization and
 b) the phylogenetically newer basis pontis which develops later.
 Alar and basal plates, with their afferent and efferent nuclei, lie medial
and lateral to the sulcus limitans , respectively.
 Cortically-originating fibers synapse on nuclei of the basis pontis (which
migrate there from the alar plate)[cortico-pontine tract]

 \\
Cerebellar Development.
 The cerebellum is first noted at 5-6 weeks as
the rhombic lips of the cranial edge of the
thinned roof of the 4th ventricle of the
hindbrain.
 The lips develop from the dorsolateral
portions of the alar plates forming the
cerebellar primordia.
 Growth causes the 2 rhombic lips to fuse in
the midline to form the cerebellar plate which
covers the 4th ventricle caudal to the
mesencephalon.
Development of the Cerebellum
Cerebellar dvpmnt contd.
 The fused rhombic lips assume a dumbbell shape -
the central unpaired part is the vermis while the
lateral knobs are the hemispheres.
 By the end of the 4th month growth causes fissures
on the surface.
 The first fissure to develop is the posterolateral
fissure which separates the flocculonodular lobe
from the corpus cerebelli which is rostral to it.
 The corpus cerebelli grows more rapidly than the
flocculonodular lobes and becomes divided by the
primary fissure into the anterior and posterior lobes.
 The surface of the lobes are further marked by the
development of many closely packed transverse
gyri called folia.
Cerebellar development
Histogenesis of the cerebellum
 Histogenesis of the cerebellar cortex - In the 2nd month of
development the cerebellum consists of a ventricular (inner
germinal layer), mantle, and marginal zones.
 By 19 weeks neuroblasts dividing in inner germinal layer
migrate to the marginal layer, proliferate and form the
external granular (germinal) layer.
 The outer germinal layer produces basket, granule and
stellate cells.
 The inner germinal layer produces the Purkinje and Golgi
cells and the cells of the deep cerebellar nuclei (dentate,
globose, emboliform and fastigii).
 Radial glial cells extend from the ventricular layer to the
surface of the marginal layer and guide the migration of the
developing neurons.
 Neuroblasts of both dividing cell layers produce glia.
Development of the Midbrain
Mesencephalon
 The adult mesencephalon (midbrain) is the least modified of the brainstem
structures with regard to basal and alar plates.{MOST IMPORTANT AS
FAR AS BEHAVIOUR IS CONCERNED}
 Neuroblasts of alar plates migrate to form inferior and superior colliculi
(tectum-corpora quadrigemina).
 Inferior and superior colliculi are related to the auditory and visual systems
respectively.
 The general somatic afferent portion of CN V, the mesencephalic nucleus, is
also found here.
 Oculomotor neurons (GSE) arise from mesencephalic neuroblasts while
trochlear motor (GSE) neurons migrate to this location from the
metencephalon[ remember: medial longitudinal fasciculus].
 The basal plates and the floor plate expand.
 They form the tegmentum of the cerebral peduncles in which the motor
nuclei of CN III and IV are found in the central gray along with the general
visceral efferents to the eye i.e., the Edinger-Westphal nucleus.
 Corticofugal fiber tracts help form
ventrolateral bulges of the cerebral
peduncles.
 The embryologic origin of the red nucleus and
substantia nigra (from alar or basal plates) in
the cerebral peduncles are uncertain.
 The cavity of the original neural tube is little
modified in the adult midbrain except to be
narrowed by growth of the surrounding
midbrain structures; it remains as the narrow
cerebral aqueduct.
Development of the
Diencephalon/Telencephalon
 The structure of the early prosencephalon closely resembles the
early neural tube i.e., thick lateral walls are connected by thinner
floor and roof plates.
 The early prosencephalon develops an ocular cup from its
ventrolateral walls in the position of the future diencephalon.
 In the 5th week, when the embryo reaches the 7 mm stage, the
simple plan of the prosencephalon changes; paired telencephalic
vesicles and the diencephalon begin to form; the optic cup
continues its development.
 Rapid bilateral expansion of the telencephalon results in
rearward overgrowth of the diencephalon.
 An early separation of the telencephalon and diencephalon
occurs through a shallow tele-diencephalic sulcus which deepens
and persists in the adult as the horizontal transverse cerebral
fissure (filled with duplicated pia and blood vessels, called velum
interpositum).
 As development progresses the growing hemispheres continue
their caudal expansion so as to cover the mesencephalon
Development of the
Diencephalon/Telencephalon
Development of the
Diencephalon/Telencephalon
 In the embryo, as in the adult, the roof of the diencephalon is very thin
comprised only of ependyma plus adjacent pia called the tela choroidea.
 When blood vessels invade the tela choroidea the choroid plexus of the
3rd (and lateral) ventricles develop and invade the ventricles.
 The thin medial wall of the ventricle is the choroid fissure; its most
rostral point is at the interventricular foramen. In the adult the choroid
fissure is “C”-shaped and continuous in the medial walls of the parietal
and temporal lobes.
 Early in development, the diencephalon develops 2 pairs of prominent
swellings in the walls of the 3rd ventricle.
 The swellings represent only the alar plate; there is no basal plate.
 The largest mass is the thalamus dorsally, separated by the
hypothalamic sulcus from the ventral hypothalamus.
 Where the roof plate thickens along the medial wall of the thalamus
are the smaller swellings of the epithalamus comprised of the a)
midline pineal gland, b) paired habenular nuclei, and c) paired stria
medullaries.
Development of the
Diencephalon/Telencephalon
Other diencephalic structures
 The lamina terminalis (represents the membrane formed at the point of
closure of the anterior neuropore) is the most rostral structure of the
early telencephalon.
 By 10 weeks it contains the rudiments of the commissural bundles i.e.,
corpus callosum, optic chiasm and anterior commissure.
 The lamina terminalis provides the only location where nerves
interconnect the cerebral hemispheres.
 Crossing fibers of the optic chiasm develop in the lamina ventrally, the
anterior commissure connects olfactory bulbs and temporal lobes, the
commissure of the fornix joins the hippocampal formations, and most
dorsally is the corpus callosum which connects non-olfactory cortical
areas.
 Other crossing fibers do not connect the hemispheres e.g., the
posterior commissure connects preoptic areas, the habenular
commissure connects habenular nuclei.
 The interventricular foramina, which connects the 3rd ventricle with the
lateral ventricles, lies just caudal to the lamina terminalis.).
 The stria medullaris and tela choroidea form the roof of the 3rd
ventricle.
Development of the
Diencephalon/Telencephalon
Corpus callosum
 The largest commissural bundle is the corpus callosum.
 It begins as a small bundle but it grows as the cerebral
hemispheres expand, encircling the diencephalon and
becoming “C”-shaped.
 First, the hemispheres form parietal and frontal lobes;
posterior expansion next forms occipital lobes followed by
growth in an inferior direction producing temporal lobes.
 By its caudalward growth the hemispheres arch over the
tela choroidea and choroid plexus of the roof of the
diencephalon.
 This “C”-shaped expansion causes many underlying
structures to also become “C”-shaped e.g., corpus
callosum, lateral ventricle, choroid plexus, caudate nucleus,
fornix.
 The insula is a lobe of the brain that remains relatively
undeveloped as it retains a fixed position while the rest of
the hemisphere grows around and over it.
 Early in development hippocampal ridges form on the
medial aspect of the telencephalic vesicles.
 These ridges are joined by the commissure of the fornix.
 When the temporal lobes grow downward and forward in
the older embryo, the hippocampal formation forms a ring
of gray matter (just above the choroid fissure) on the
medial aspect of the hemispheres which is continuous with
the “C”-shaped fornix.
 As both the fornix and corpus callosum grow rearward they
become separated and the tissue remaining between them
is the septum pellucidum.
 The anterior commissure connect olfactory bulbs and
anterior temporal lobes.
Development of the
Diencephalon/Telencephalon
 The corpus striatum is comprised of two structures a) caudate-
putamen and b) globus pallidus.
 In the adult the caudate and putamen are partially separated by
fibers of the anterior limb of the internal capsule.
 The posterior limb of the internal capsule separates the globus
pallidus from the diencephalon (thalamus).
 Early in the development of the cerebral vesicles.
 The caudate-putamen develops from neuroblasts of the floor of
the developing telencephalic vesicle called the striatal ridge
while the globus pallidus originates from neuroblasts in the wall
of the 3rd ventricle of the diencephalon.
 Pallidal neuroblasts eventually migrate laterally to join the
caudate-putamen.
 Both parts of the corpus striatum originate near the foramen of
Monro.
 At first, during the caudal expansion of the telencephalic vesicles,
the hemispheres are separate from the diencephalon (except at
the foramen of Monro).
Development of the
Diencephalon/Telencephalon
 Later, when the hemispheres begin their complex bending,
the medial aspects of the growing hemispheres approach
the diencephalon and their apposing surfaces fuse.
 After the fusion, corticofugal fibers heading to and from
the cerebral cortex incompletely divide the caudate nucleus
from the putamen.
 Later, then putamen merges with the globus pallidus
forming the lenticular nucleus.
 As the hemisphere grows backward, the body of the
caudate nucleus portion of the striatal ridge in the floor of
the lateral ventricle follows the wall of the developing
lateral ventricle downward into the roof of the inferior horn
of the lateral ventricle where it forms the tail of the caudate
nucleus.
Development of the
Diencephalon/Telencephalon
Fetal neurogenesis
 The layered structure of the adult cerebral cortex forms
from the telencephalon as the surface area increases. At
first there are 3 zones to the cortex:
 1) germinal zone, immediately surrounding the lateral
ventricle,
 2) intermediate zone, becomes the white matter, and
 3) marginal zone, becomes the gray matter.
 Neuroblasts of the germinal zone divide and migrate into
the marginal zone to become neurons and glial cells.
 The marginal zone is formed by cells migrating a) early,
which become the deeper layers of the cortex while those
that migrate b) later, form the more superficial layers.
 Between 6 and 8 months 6 layers are observed in the marginal
zone of the neocortex, recognized by cellular and fiber laminae.
 The 6-layered cortex is further distinguished as having two main
divisions:
 1) the deeper highly cellular pyramidal layer are layers II - VI and
 2) the more superficial molecular layer (layer I) is comprised
mostly of fibers.
 The intermediate zone becomes the white matter of the cerebral
hemispheres which is traversed by the processes of the cells
migrating toward the surface.
 At birth the neocortex has a 6-layered structure while cortical
areas dealing with olfaction (paleocortex) and the hippocampal
formation (archicortex) do not have a six-layered structure.
Development of the
Diencephalon/Telencephalon
 Early in the development e.g., 12 weeks, of
the cerebral hemispheres the surface is
smooth, without sulci.
 The various lobes of the brain are present.
 By about 7 months rapid growth of the
hemispheres results in the development of
gyri and sulci.
 At birth, the main gyri and sulci of adult brain
are recognized.
Development of the
Ventricular System (Late)
 The pattern of the ventricular system is established early.
 The prosencephalon separates into 2 expanding telencephalic
vesicles (lateral ventricles) and a slit-like diencephalic vesicle (3rd
ventricle).
 Thickening of its walls narrows the lumen of this segment to a
vertical slit, the 3rd ventricle.
 The lumina of the lateral and 3 ventricles connect just behind the
lamina terminalis via the paired foramina of Monro.
 Expansion of the mesencephalon narrows its vesicle forming the
cerebral aqueduct, which connects the 3rd and 4th ventricle of
the rhombencephalon.
 The rhombencephalic roof is thin and covers the 4th ventricle
which forms a shallow, diamond-shaped depression.
 The expansion of the cerebral hemispheres affects the shape of
the lateral ventricles which become “C”-shaped.
Development of the Choroid
Plexus
Choroid plexus

 A rich capillary plexus develops in the

connective tissue around the neural tube of
the 6-8 mm embryo.
 The roofs of the prosencephalon and
rhombencephalon are thin, composed of
ependyma that becomes invaded by the
capillaries.
 Ependyma plus pia mater is called tela
choroidea; vascularized tela choroidea is
choroid plexus.
 “Holoprosencephaly” is an anomaly resulting from
disturbances of early forebrain development.
 Because of the influence of the brain on surrounding
structures facial defects are common.
 Fully developed cases frequently include facial defects,
microcephaly, and closely set eyes.
 Cyclopia: During early normal development the eye fields
form on either side of the diencephalon.
 Failure of development of the ventral midline portion of
the prosencephalon allows the eye fields to form in close
proximity to one another resulting in cyclopia.
 In the example shown, the near absence of upper and mid-
facial tissue allowed the fusion of the optic primordia below
a tubular proboscis (nose).
Development of the Eye
Cyclopia
Defects
 Anencephaly;
 Hydrocephaly;
 Hydramcepahaly;
 Spina bifida cystica / occulta /with/without
meningocele or myelomeningocele;
 Lissencephaly- absence of gyri;
 Microcephaly;
 Machiafava-Bignami Syndrome;
 Craniosynostosis;
 Myeloschisis ;