The document summarizes key stages in the embryological development of the nervous system and special senses. It describes how the neural plate forms and folds to become the neural tube. It then discusses the formation of the three germ layers and how neural induction occurs. It provides details on neurulation and neural tube formation, as well as common defects that can arise. It also summarizes the development of the main divisions and structures of the brain and spinal cord.

1. EMBRYOLOGICAL DEVELOPMENT OF
THE NERVOUS SYSTEM AND SPECIAL
SENSES
PRESENTER: DR PASHI V M
MODERATOR: PROF MUNKONGE

2. • Neurulation
• The notochord induces overlaying ectoderm
to become neuroectoderm and form a neural
tube. The following stages of neural tube
formation are evident:
• neural plate—ectodermal cells overlaying the
notochord become tall columnar, producing a
thickened neural plate (in contrast to
surrounding ectoderm that produces
epidermis of skin).

3. • neural groove—the neural plate is
transformed into a neural groove.
• neural tube—the dorsal margins of the neural
groove merge medially, forming a neural tube
composed of columnar neuroepithelial cells
surrounding a neural cavity.
• In the process of separating from overlaying
ectoderm, some neural plate cells become
detached from the tube and collect bilateral
to it, forming neural crest.

5. The three germ layers are formed at
gastrulation
Ectoderm: outside, surrounds other
layers later in development,
generates skin and nervous
tissue.
Mesoderm: middle layer, generates
most of the muscle, blood and
connective tissues of the body
and placenta.
Endoderm: eventually most interior
of embryo, generates the
epithelial lining and associated
glands of the gut, lung, and
urogenital tracts.

6. Neural Induction:
In addition to patterning the forming mesoderm, the
primitive node also sets up the neural plate
• Ectoderm exposed to
BMP-4 (from endoderm
and mesoderm below),
develops into skin
• However, the node
secretes BMP-4
antagonists: (e.g.
noggin, chordin, &
follistatin) that allow a
region of the ectoderm
to develop into nerve
tissue.

7. Neurulation: folding of the neural
plate
1.Median hinge point forms (probably
due to signaling from notochord) –
columnar cells adopt triangular
morphology (apical actin constriction,
like a purse string)
2.Lateral hinge point forms by a similar
mechanism (probably due to
signaling from nearby mesoderm).
3.As neural folds close, neural crest
delaminates and migrates away
(more on that later…)
4.Closure happens first in middle of the
tube and then zips rostrally and
caudally.

8. Neurulation:
folding and closure of the neural plate
• Folding and closure of the
neural tube occurs first in the
cervical region.
• The neural tube then “zips” up
toward the head and toward
the tail, leaving two openings
which are the anterior and
posterior neuropores.
• The anterior neuropore closes
around day 25.
• The posterior neuropore
closes around day 28.

9. Failure of neuropores to close can cause
neural tube defects
anterior neuropore: anencephaly
posterior neuropore: spina bifida

13. • Failure of the anterior neuropore to close
results in anencephaly In this defect, the brain
is not formed, the surrounding meninges and
skull may be absent, and there are facial
abnormalities.
• The defect extends from the level of the lamina
terminalis , the site of anterior neuropore
closure, to the region of the foramen magnum .
• An encephalocele is a herniation of intracranial
contents through a defect in the cranium (
cranium bifidum ).

14. • The cystic structure may contain only
meninges (meningocele ), meninges plus brain
(meningoencephalocele ), or meninges plus
brain and a part of the ventricular system
(meningohydroencephalocele ).
Encephaloceles are most common in the
occipital region,
• but they may also occur in frontal and parietal
locations

17. SPINAL CORD
• Neuro tissue development
• The neuro tube is made up of neuro epithelial
cells that divide and form the neuroepithelium
• Some cell divisions are differential, producing
neuroblasts
• which give rise to neurons or glioblasts
(spongioblasts) which give rise to glial cells
• Neuroblasts and glioblasts lose contact with
surfaces of the neural tube and migrate
toward the centre of the neural tubewall.

18. • Accumulated neuroblasts and glioblasts form the
mantle layer, a zone of high cell density in the
wall of the neural tube.
• Cells that remain lining the neural cavity are
designated ependymal cells; they form an
ependymal layer. Surrounding the mantle layer, a
cell sparse zone where axons of neurons and
some glial cells are present is designated the
marginal layer.
• The mantle layer becomes gray matter
• Marginal layer becomes white matter of the
CNS.

20. The developing neural tube is divided
into 4 plates
• Roof plate: signaling
center (BMPs and
Wnts)
• Alar plate: sensory
• Basal plate: motor
• Floor plate: signaling
center (Shh)

21. • The lateral wall of the neural tube is divided
into two regions (plates).
• A bilateral indentation evident in the neural
cavity (the sulcus limitans) serves as a
landmark to divide each lateral wall into an
alar plate (dorsal) and a basal plate (ventral).
Midline regions
• dorsal and ventral to the neural cavity
constitute, respectively, the roof plate and the
floor plate.

23. Spinal cord development
• The neural cavity becomes central canal lined
by ependymal cells;
• Growth of alar and basal plates, but not roof
and floor plates, results in symmetrical right
and left halves separated by a ventral median
fissure and a dorsal median fissure (or
septum);
• The mantle layer develops into gray matter,
• The marginal layer becomes white matter

25. Regression” of the spinal cord
The spinal cord and the vertebral column are the
same length up until the 3rd month.
As each vertebral body grows thicker, the overall
length of the vertebral column begins to exceed
that of the spinal cord such that , in the adult
the spinal cord terminates at L2 or 3 and the
dural sac ends at about S2.
The tail end of the dural sac covering the spinal
cord and nerve roots remains attached at the
coccyx and becomes a long, thin strand called
the filum terminale.
Sometimes, the spinal cord can become
“tethered” or attached to the dural sac or filum
terminale; this pulls on the cord and can
obstruct flow of CSF thus causing swelling of the
ventricles of the brain (hydrocephalus),

26. CNS CELLS

27. NEURAL CREST CELLS
• the “4th germ layer” At the time of neurulation, cells at
the lateralmost edge of the neural
plate are exposed to a unique
combination of factors from the
adjacent skin, underlying mesoderm,
and from the rest of the neural plate
and are induced to form neural
crest.
The neural crest cells downregulate
cadherin expression and delmainte
from the neuroepithelium, i.e., they
transform from epithelial cells into
migratory mesenchymal cells that
contribute to forming MANY tissues
in the body.

28. Major Derivatives of the Neural Crest

30. Trunk Neural Crest:
sensory lineage
• Migrate along ventrolateral
stream and stop just medial to
somite
• Aggregate into dorsal root ganglia
and separate into 2 general
lineages:
– Sensory neurons (Wnts, NGFs,
bHLHs (Ngn1, etc.)
– Glia (Schwann cells and satellite
cells) via GDNF signaling
• Sensory neurons extend
processes in two directions:
dorsomedially to neural tube and
ventrolaterally into growing
spinal nerve (established by
outgrowth of motor neuron axons
from the ventral horn)

31. Innervation is segmental (dermatomes)

32. Sensory neurons send axons into dorsal horn.
Motor neurons send axons out of vental horn.
Axons of peripheral nerves are
myelinated by Schwann cells

33. Trunk Neural Crest:
sympathoadrenal lineage
• Migrate along ventral stream
• Dependent on expression of
Phox-2 and Mash-1
• BMPs from aorta play further
instructive role to specify bi-
potential progenitors:
– Sympathetic ganglion neurons:
induced by presence of FGF
and NGF in symp. Ganglia
– Adrenal chromaffin cells:
induced by glucocorticoids in
adrenal gland

34. Circumpharyngeal Neural Crest:
vagal crest
• Migrate caudal to 6th arch and then
become associated with wall of
fore-, mid-, and proximal hindgut
• Downregulate expression of Robo,
a Slit-2 receptor, which allows them
to invade the gut wall.
• Hand2 influences differentiation
into cholinergic phenotype

35. Innervation of the Gut:
vagal and lumbosacral crest
• Vagal crest: innervate gut wall from foregut to ~proximal 2/3 of transverse colon in hindgut
• Sacral crest: innervate hindgut wall from ~distal 1/3 of transverse colon to rectum

36. Circumpharyngeal Neural Crest:
• Associated with arches 3,4,6
• Contribute to thyroid, parathyroid, and thymus
• Cardiac crest contributes to outflow tract cushions
• Disturbances (e.g. DiGeorge syndrome, Hoxa-3 mutation) therefore have multiple
effects: craniofacial (jaw) defects, glandular defects, & outflow tract defects

37. Cranial Neural Crest:
Contribute to forehead, face, jaw, and pharyngeal arch derivatives

38. THE BRAIN
• Divided into brain stem and higher centres
• Distinct basal and Alar plates
• found on each side of the midline in the
rhombencephalon and mesencephalon.
• In the prosencephalon the alar plates are
accentuated and the basal plates regress

39. Primary Brain Vesicles
• The cranial end of the neural tube forms three
vesicles (enlargements) that further divide
into the five primary divisions of the brain.
• Caudal to the brain the neural tube develops
into spinal cord.
• Flexures: During development, the brain
undergoes three flexures which generally
disappear

41. • The midbrain flexure occurs at the level of the
midbrain.
• The cervical flexure appears at the junction
between the brain and spinal cord
• The pontine flexure is concave dorsally (the
other flexures are concave ventrally).

42. Primary brain vesicles

43. Secondary Brain Vesicles
• During the fifth week, the three primary brain
vesicles are
• divided into five secondary brain vesicles.
• This requires two additional flexures.
• The pontine flexure divides the hindbrain into
the myelencephalon caudally and the
metencephalon rostrally.
• The mesencephalon does not partition
further.

44. • The telencephalic flexure (shortened here
from the longer term diencephalic-
telencephalic sulcus ) divides the forebrain
into the diencephalon caudally and the
telencephalon rostrally.
• The telencephalon (meaning “end-brain”)
forms as an outpocketing of the forebrain and
expands enormously, with its complex lobes,
gyri, and sulci, to become the largest part of
the brain

45. Major divisions of the developing brain:
3 parts, then 5 parts
• 3 parts: Prosen-, Mesen-, and Rhomencephalon
• 5 parts: Prosencephalon divides into telen- and diencephalon,
Rhombencephalon divides into met- and myelencephalon

46. Major divisions of the developing brain:
3 parts, then 5 parts

47. Hindbrain: Medulla oblongata and pons
• alar plates move laterally and the cavity of the
neural tube expands dorsally forming a fourth
ventricle;
• the roof of the fourth ventricle (roof plate) is
stretched and reduced to a layer of
ependymal cells covered by pia mater;
• a choroid plexus develops bilaterally in the
roof of the ventricle and secretes
cerebrospinal fluid;

48. • the basal plate (containing efferent neurons of
cranial nerves) is positioned medial to the alar
plate and ventral to the fourth ventricle;
• white and grey matter (marginal & mantle
layers) become intermixed (unlike spinal cord);
• Cerebellar development adds extra structures.

49. Hind brain

51. Development of the myelencephalon
• Alar plate develops into 4 sensory tracts:
– Olivary nucleus (cerebellar input)
– Somatic afferent (general sensation from the face, via CN V, external ear, auditory meatus, and eardrum
via CN IX, X)
– Special visceral afferent (taste, CN IX, X)
– General visceral afferent (autonomic input, CN IX, X)
• Basal plate develops into 3 motor tracts:
– General visceral efferent (autonomic output, CN IX, X)
– Special visceral efferent (innervation of pharyngeal arch muscles of the larynx & pharynx, CN IX, X, XI)
– Somatic efferent (innervation of skeletal muscles of the tongue, CN XII)
(covered by ependymal cells that produce CSF)

52. Midbrain
• the neural cavity of the midbrain becomes
mesencephalic aqueduct (which is not a
ventricle because it is completely surrounded
by brain tissue and thus it lacks a choroid
plexus).

53. • alar plates form two pairs of dorsal bulges
which become rostral and caudal colliculi
(associated with visual and auditory reflexes,
respectively);
• the basal plate gives rise to oculomotor (III)
and trochlear (IV) nerves which innervate
muscles that move the eyes.
• Note: The midbrain is the rostral extent of the
basal plate (efferent neurons).

54. Development of the mesencephalon
• Alar plate generates superior and inferior colliculi
– Inferior colliculus: auditory relay
– Superior colliculus: visual relay
• Basal plate generates 4 motor tracts:
– Somatic efferent (motor output to extraocular muscles, CN III, IV)
– Visceral efferent (motor output to ciliary ganglion of the eye, CN III)
– Red nucleus (motor relay to flexor muscles of the upper limb)
– Substantia nigra (dopaminergic output to the basal ganglia of the telencephalon)

55. Forebrain
• derived entirely from alar plate
Diencephalon:
• the neural cavity expands dorsoventrally and
becomes the narrow third ventricle, the roof
plate is stretched and choroid plexuses
develop bilaterally in the roof of the third
ventricle and secrete cerebrospinal fluid;
• the floor of the third ventricle gives rise to the
neurohypophysis (neural lobe of the pituitary
gland);

57. • the mantle layer of the diencephalon gives
rise to thalamus, hypothalamus, etc.; the
thalamus enlarges to the point where right
and left sides meet at the midline and
obliterate the center of the third ventricle.
• the optic nerve develops from an outgrowth
of the wall of the diencephalon.

58. Telencephalon (cerebrum):
• bilateral hollow outgrowths become right and
left cerebral hemispheres; the cavity of each
outgrowth forms a lateral ventricle that
communicates with the third ventricle via an
interventricular foramen (in the wall of each
lateral ventricle, a choroid plexus develops
that is continuous with a choroid plexus of the
third ventricle via an interventricular
foramen);

59. • at the midline, the rostral end of the
telencephalon forms the rostral wall of the
third ventricle (the wall is designated lamina
terminalis);
• the mantle layer surrounding the lateral
ventricle in each hemisphere gives rise to
basal nuclei and cerebral cortex;

60. Development of the diencephalon
• Pineal gland: sleep-wake cycle, secretes
melatonin
• Epithalamus: masticatory and swallowing
functions
• Thalamus: major relay of sensory input to
cerebral cortex
• Hypothalamus: master regulatory center
(autonomic and endocrine) and also limbic
system (emotion & behavior)
• Hypophysis/infundibulum: posterior pituitary
gland, secretes ADH and oxytocin
• Optic cup: retina of eye

61. Ventricular System
• The ventricular system is an elaboration of the
lumen of cephalic portions of the neural tube,
and its development parallels that of the
brain.
• The cavities of the telencephalic vesicles
become the lateral ventricles ;
• The diencephalic cavity becomes the third
ventricle ;
• The rhombencephalic cavity becomes the
fourth ventricle .

62. • The cavity of the mesencephalon becomes the
narrow cerebral aqueduct ( of Sylvius )
connecting the third and fourth ventricles,
• The openings between the lateral ventricles and
the third ventricle become the intraventricular
foramina ( of Monro ).
• The ventricular system is lined with ependymal
cells .
• Each ventricle originally has a thin roof composed
of an internal layer of ependyma and an outer
layer of delicate connective tissue ( pia mater ).
• In each ventricle, blood vessels invaginate this
membrane to form the choroid plexus .

64. • Openings that arise in the caudal roof of the
fourth ventricle during development form a
communication between the ventricular
system and the subarachnoid space.
• These are the midline medial aperture (
foramen of Magendie ) and the paired lateral
foramina of Luschka .
• Although these foramina develop slowly, they
are patent by the end of the first trimester.
• CSF is produced mainly by the choroid
plexuses of the lateral and third ventricles.

65. • It escapes the ventricular system through
foramina of the fourth ventricle and passes
into the subarachnoid space.
• From there, it is absorbed into the venous
system through the arachnoid villi located
primarily in the superior sagittal sinus.
• If the flow of CSF through the ventricles is
obstructed during
• prenatal development, the ventricular system
can become markedly
• dilated, a condition called congenital
hydrocephalus

66. HYDROCEPHALUS

67. Formation of Meninges
• Meninges surround the CNS and the roots of
spinal and cranial nerves.
• Three meningeal layers (dura mater,
arachnoid, and pia mater) are formed as
follows:
• mesenchyme surrounding the neural tube
aggregates into two layers;
• the outer layer forms dura mater;
• cavities develop and coalesce within the inner
layer, dividing it into arachnoid and piamater;
the cavity becomes the subarachnoid space
which contains cerebrospinal fluid.

69. PERIPHERAL NERVOUS SYSTEM
The peripheral nervous system develops mostly
from cells of the neural crest.
Placodes
• Specialized epidermal cells called placodes
are found in the developing head region.
• These will join neural crest cells, together
placodes and neural crest form the ganglia of
cranial nerves V, VII, VIII, IX, and X.

70. Cranial Nerve Ganglia
• Cranial nerves V (trigeminal nerve), VII (facial
nerve), IX (glossopharyngeal nerve), and X
(vagus nerve) have sensory ganglia that
originate from neural crest and placode cells
• They contain pseudounipolar cell bodies.
• These are the trigeminal or semilunar (V)
ganglion, the geniculate ganglion (VII), the
superior and inferior (IX) ganglia of the
glossopharyngeal nerve, and the jugular
• and nodose (X) ganglia of the vagus nerve.

71. Spinal nerves
• Posterior (Dorsal) Root Ganglia
• Pseudounipolar cells of posterior , or dorsal ,
root ganglia are derived from the neural crest.
• Each spinal nerve and its corresponding
ganglion are associated with a segment (or
somite ) of the developing embryo.

72. • The segmental nature of the embryo is
reflected in the segmental sensory innervation
of the body
• These segments, known as dermatomes , are
• important in the diagnosis of many neurologic
disorders.

74. Innervation is segmental (dermatomes)

75. Visceral Motor System
• The postganglionic sympathetic and
parasympathetic neurons of the visceral
motor system are also derived from the neural
crests.
• Some of these cells remain near their site of
origin to form the sympathetic chain ganglia
adjacent to the vertebral column.
• Other cells migrate with branches of the aorta
to form the sympathetic prevertebral ganglia .

76. • Most of the autonomic (visceromotor)
neurons of the digestive tract ( Auerbach and
Meissner plexuses) are formed by neural crest
cells that migrate from the area of the
rhombencephalon.
• Consequently, these cells receive vagal
innervation in the adult.
• Visceromotor (autonomic) neurons of the
descending colon and pelvic structures are
derived from neural crest cells that arise from
sacral cord levels during secondary
neurulation

77. • The human syndrome congenital megacolon (
Hirschsprung
• disease ). neurons forming the enteric ganglia
fail to migrate into the lower
• bowel. In the absence of these cells, no
sensory signal indicating
• the presence of feces in the colon is sent to
the CNS. Therefore,
• no motor signal is sent to control defecation.

78. Trunk
Neural
Crest:
sympathetic
nervous system

79. Parasympathetic
Nervous System:
derived from
cranial, vagal, and
lumbosacral crest

80. Special senses
Formation of the Eye
• The developing eye appears in the 22-day
embryo
• as a pair of shallow grooves on the sides of
the forebrain
• Both eyes are derived from a single field of the
neural plate.
• The single field separates into bilateral fields
associated with the diencephalon.

82. • The following events produce each eye:
• a lateral diverticulum from the diencephalon
forms an optic vesicle attached to the
diencephalon by an optic stalk;
• a lens placode develops in the surface
ectoderm where it is contacted by the optic
vesicle;
• the lens placode induces the optic vesicle to
invaginate and form an optic cup while the
placode invaginates to form a lens vesicle that
invades the concavity of the optic cup;

83. • an optic fissure is formed by invagination of
the ventral surface of the optic cup and optic
stalk, and a hyaloid artery invades the fissure
to reach the lens vesicle;
• The optic cup forms the retina and contributes
to formation of the ciliary body and iris.
• The outer wall of the cup forms the outer
pigmented layer of the retina, and the inner
wall forms neural layers of the retina.
• The optic stalk becomes the optic nerve as it
fills with axons traveling from the retina to the
brain.

87. • The lens vesicle develops into the lens,
consisting of layers of lens fibers enclosed
within an elastic capsule.
• The vitreous compartment develops from the
concavity of the optic cup, and the vitreous
body is formed from ectomesenchyme that
enters the compartment through the optic
fissure.
• ectomesenchyme (from neural crest)
surrounding the optic cup condenses to form
inner and outer layers, the future choroid and
sclera, respectively;

90. • the ciliary body is formed by thickening of
choroid ectomesenchyme plus two layers of
epithelium derived from the underlying optic
cup;
• the ectomesenchyme forms ciliary muscle and
the collagenous zonular fibers that connect
the ciliary body to the lens;
• the iris is formed by choroid ectomesenchyme
plus the superficial edge of the optic cup;
• The outer layer of the cup forms dilator and
constrictor muscles and the inner layer forms
pigmented epithelium;

93. • the ectomesenchyme of the iris forms a
pupillary membrane that conveys an anterior
blood supply to the developing lens;
• when the membrane degenerates following
development of the lens, a pupil is formed;
• the cornea develops from two sources: the
layer of ectomesenchyme that forms sclera is
induced by the lens to become inner
epithelium and stroma of the cornea, while
surface ectoderm forms the outer epithelium
of the cornea;

94. • the anterior chamber of the eye develops as a
cleft in the ectomesenchyme situated
between the cornea and the lens;
• the eyelids are formed by upper and lower
folds of ectoderm, each fold includes a
mesenchyme core;
• the folds adhere to one another but they
ultimately separate prenatally.
• ectoderm lining the inner surfaces of the folds
becomes conjunctiva, and lacrimal glands
develop by budding of conjunctival ectoderm;

95. • skeletal muscles that move the eye
(extraocular eye mm.) are derived from rostral
somitomeres
• (innervated by cranial nerves III, IV, and VI).

96. Formation of the Ear
• The ear has three components: external ear,
middle ear, and inner ear.
• The inner ear contains sense organs for
hearing (cochlea) and detecting head
acceleration (vestibular apparatus),
• the latter is important in balance.
• Innervation is from the cochlear and
vestibular divisions of the VIII cranial nerve.

99. • The middle ear contains bones (ossicles) that
convey vibrations from the tympanic
membrane (ear drum) to the inner ear.
• The outer ear channels sound waves to the
tympanic membrane.

100. Inner ear:
• an otic placode develops in surface ectoderm
adjacent to the hindbrain; the placode
invaginates
• to form a cup which then closes and separates
from the ectoderm, forming an otic vesicle
(otocyst);
• an otic capsule, composed of cartilage,
surrounds the otocyst;
• some cells of the placode and vesicle become
neuroblasts and form afferent neurons of the
vestibulocochlear nerve (VIII);

105. • the otic vesicle undergoes differential growth
to form the cochlear duct and semicircular
ducts of the membranous labyrinth;
• some cells of the labyrinth become specialized
receptor cells found in maculae and ampullae;
• the cartilagenous otic capsule undergoes
similar differential growth to form the osseous
labyrinth within the future petrous part of the
temporal bone.

106. Middle ear:
• the dorsal part of the first pharyngeal pouch
• forms the lining of the auditory tube and
tympanic cavity
• the malleus and incus develop as
endochondral bones from ectomesenchyme in
the first branchial arch and the stapes
develops similarly from the second arch

108. Outer ear:
• the tympanic membrane is formed by
apposition of endoderm and ectoderm where
the first pharyngeal pouch is apposed to the
groove between the first and second branchial
arches;
• the external ear canal (meatus) is formed by
the groove between the first and second
branchial arches; the arches expand laterally
to form the wall of the canal and the auricle
(pinna) of the external ear.

110. • Taste buds
• Taste buds are groups of specialized
(chemoreceptive) epithelial cells localized
principally on papillae of the tongue.
• Afferent innervation is necessary to induce
taste bud formation and maintain taste buds.
• Cranial nerves VII (rostral two-thirds of
tongue) and IX (caudal third of tongue)
innervate the taste buds of the tongue.

111. Olfaction
• Olfaction (smell) involves olfactory mucosa
located caudally in the nasal cavity and the
vomeronasal organ located rostrally on the
floor of the nasal cavity.
• Olfactory neurons are chemoreceptive; their
axons form olfactory nerves (I).
• an olfactory (nasal) placode appears bilaterally
as an ectodermal thickening at the rostral end
of the future upper jaw;

112. • the placode invaginates to form a nasal pit
that develops into a nasal cavity as the
surrounding tissue grows outward;
• in the caudal part of the cavity, some
epithelial cells differentiate into olfactory
neurons;
• the vomeronasal organ develops as an
outgrowth of nasal epithelium that forms a
blind
• tube; some epithelial cells of the tube
differentiate into chemoreceptive neurons.

113. REFENCES
• Langmans’s Medical Embryology, 12th ed
• Phillip M. Ecker et al, An animated tour of
human development, version 1.1.