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embryo ch 18 and 19
Central Nervous System
CNS appears at beginning of 3rd week as slipper-shaped plate of thickened ectoderm (neural
plate) in mid-dorsal region in front of primitive node
Lateral edges elevate to form neural folds, which continue to approach each other at the
midline until they fuse, forming the neural tube – open ends of neural tube form cranial and
caudal neuropores that communicate with overlying amniotic cavity
o Closure of cranial neuropore proceeds cranially from initial closure site in cervical
region, and from a site in the forebrain that forms later
o Later site proceeds cranially to close rostral-most region of neural tube and caudally to
meet advancing closure from cervical site
Final closure of cranial neuropore occurs at 18-20 somite stage (about 25th day)
Cephalic end of neural tube shows 3 dilations called primary brain vesicles
o Prosencephalon (forebrain)
o Mesencephalon (midbrain)
o Rhombencephalon (hindbrain)
Simultaneously, cephalic end of neural tube forms 2 flexures
o Cervical flexure – at junction of hindbrain and spinal cord
o Cephalic flexure – in midbrain region
When embryo is 5 weeks old, prosencephalon consists of
o Telencephalon – formed by midportion and 2 lateral outpocketings (primitive cerebral
o Diencephalon – characterized by outgrowth of optic vesicles
Rhombencephalic isthmus – deep furrow that separates mesencephalon from
Rhombencephalon consists of
o Metencephalon – later forms pons and cerebellum
o Myelencephalon
o Pontine flexure – boundary between above 2 portions
Lumen of spinal cord (central canal) is continuous with that of brain vesicles
o Cavity of rhombencephalon is 4th ventricle, that of diencephalon is 3rd ventricle, and
those of cerebral hemispheres are lateral ventricles
o Lumen of mesencephalon connects 3rd and 4th ventricles – lumen becomes very narrow
here and is known as aqueduct of Sylvius
o Each lateral ventricle communicates with 3rd ventricle through interventricular foramina
of Monro
Spinal Cord
Neuroepithelial cells – constitute walls of recently closed neural tube
o Extend over entire thickness of wall and form thick pseudostratified epithelium
o Junctional complexes at lumen connect them
During neural groove stage and immediately after closure of tube, neuroepithelial cells divide
rapidly, producing more and more neuroepithelial cells collectively called neuroepithelial layer
or neuroepithelium
once neural tube closes, neuroepithelial cells begin to give rise to neuroblasts (primitive nerve
cells with a large round nucleus, pale nucleoplasm, and a dark-staining nucleolus)
Neuroblasts form mantle layer around neuroepithelial layer – mantle later becomes gray matter
of spinal cord
Marginal layer – contains nerve fibers emerging from neuroblasts in mantle layer – as a result of
myelination of nerve fibers, this layer takes on white appearance – white matter of spinal cord
As a result of continuous addition of neuroblasts to mantle layer, the neural tube shows ventral
and dorsal thickening
o Ventral thickenings (basal plates) contain ventral motor horn cells
o Dorsal thickenings (alar plates) form sensory areas
Sulcus limitans – longitudinal groove that marks boundary between basal plates and alar plates
Dorsal and ventral midline portions of neural tube called roof and floor plates, respectively
o Do not contain neuroblasts and serve primarily as pathways for nerve fibers crossing
from one side to the other
Intermediate horn – group of neurons accumulating between ventral motor horn and dorsal
sensory horn – contains neurons of sympathetic portion of ANS and is only in thoracic and upper
lumbar (L2 or L3) levels of spinal cord
Histological differentiation
Neuroblasts – arise exclusively by division of neuroepithelial cells
o Initially have central process extending to lumen (transient dendrite), but when they
migrate into mantle layer, this process disappears and neuroblasts temporarily round
and apolar
o With further differentiation, 2 new cytoplasmic processes appear on opposite sides of
cell body, forming bipolar neuroblasts
o Process at one end of cell elongates to form primitive axon, while the other end shows
number of cytoplasmic arborizations (primitive dendrites)
o Cell is then known as multipolar neuroblasts
o These develop into neurons
o Once they are actual neuroblasts, they lose their ability to divide
Axons of neurons in basal plate break through marginal zone and become visible on ventral
aspect of cord (called collectively ventral motor root of spinal nerve)
Axons of neurons in dorsal sensory horn penetrate into marginal layer of cord, where they
ascend to either higher or lower levels to form association neurons
Gliablasts – majority of primitive supporting cells – formed by neuroepithelial cells after
production of neuroblasts ceases
o Migrate from neuroepithelial layer to mantle and marginal layers
In mantle, they differentiate into protoplasmic astrocytes and fibrillar astrocytes – these
situated between blood vessels and neurons where they provide support and serve
metabolic functions
Oligodendroglial cell – formed from gliablasts found primarily in marginal layer – forms myelin
sheaths around ascending and descending axons in marginal layer
Microglial cell – highly phagocytic cell type derived from vascular mesenchyme when blood
vessels grow into CNS
When neuroepithelial cells cease to produce neuroblasts and gliablasts, they differentiate into
ependymal cells lining central canal of spinal cord
During elevation of neural plate, group of cells appears along each edge (crest) of neural folds –
called neural crest cells – ectodermal in origin and extend throughout length of neural tube –
migrate laterally and give rise to sensory ganglia (dorsal root ganglia)
o Neuroblasts of sensory ganglia form 2 processes – centrally growing processes
penetrate dorsal portion of neural tube
 In spinal cord, centrally growing processes either end in dorsal horn or ascend
through marginal layer to one of higher brain centers – known collectively as
dorsal sensory root of spinal nerve
 Peripherally growing processes join fibers of ventral motor roots and thus
participate in formation of trunk of spinal nerve
o Cells from neural crest also differentiate into sympathetic neuroblasts, Schwann cells,
pigment cells, odontoblasts, meninges, and mesenchyme of pharyngeal arches
Motor nerve fibers being to appear in 4th week, arising from nerve cells in basal plates of spinal
cord – collect into bundles (ventral nerve roots)
Dorsal nerve roots form as collections of fibers originating from cells in dorsal root ganglia
(spinal ganglia) – central processes from ganglia form bundles that grow into spinal cord
opposite dorsal horns and distal processes join the ventral nerve roots to form a spinal nerve
o Almost immediately, spinal nerves divide into dorsal and ventral primary rami
Schann cells myelinate peripheral nerves with each cell myelinating only a single axon
o Originate from neural crest, migrate peripherally, and wrap themselves around axons,
forming neurilemma sheath
o Around 4th month, many nerve fibers take on whitish appearance as result of deposition
of myelin, formed by repeated coiling of Schwann cell membrane around axon
Oligodendroglial cells – precursors of oligodendrocytes surrounding spinal cord nerve fibers –
single oligodendrocyte can myelinate up to 50 axons
o Some motor fibers descending from higher brain centers to spinal cord do not become
myelinated until first year of postnatal life
o Tracts in nervous system become myelinated around time they start to function
Positional Changes of Cord
in 3rd month, spinal cords extends entire length of embryo, and spinal nerves pass through
intervertebral foramina at their level of origin
with increasing age, vertebral column and dura lengthen more rapidly than neural tube, and
terminal end of spinal cord gradually shifts to higher level (around L3 at birth)
Neural Tube Defects
Spina bifida
o Meningocele – only fluid-filled meninges protrude through defect
o Myelomeningocele – neural tissue included in sac that protrudes
o Rachischisis – neural folds do not elevate, but remain as flattened mass of neural tissue
Hydrocephaly requiring intervention develops in 80%-90% of children born with severe NTDs
Arnold-Chiari malformation – herniation of part of cerebellum into foramen magnum –
obstructs flow of CSF and causes hydrocephaly
Brain stem – consists of myelencephalon, pons from metencephalon, and mesencephalon
Higher centers of brain – cerebellum and cerebrum
Brain stem also has basal and alar plates, representing motor and sensory areas – continuous
with spinal cord
Higher centers show accentuation of alar plates and regression of basal plates
Rhombencephalon – includes myelencephalon (most caudal of brain vesicles) and
metencephalon (extends from pontine flexure to rhombencephalic isthmus)
o Myelencephalon give rise to medulla oblongata – lateral walls are everted – alar and
basal plates separated by sulcus limitans
 Motor nuclei of basal plate divided into
 Medial somatic efferent group
o Contains motor neurons that form cephalic continuation of
anterior horn cells – includes hypoglossal nerve that supplies
tongue musculature
o In metencephalon and mesencephalon, column contains
neurons of nerves that supply eye musculature
 Intermediate special visceral efferent group
o Extends into metencephalon, forming special visceral efferent
motor column
o Supplies striated muscles of pharyngeal arches
o In myelencephalon, contains accessory, vagus, and
glossopharyngeal nerves
 Lateral general visceral efferent group
o Contains motor neurons that supply involuntary musculature of
respiratory tract, intestinal tract, and heart
 Alar plate contains sensory relay nuclei
Somatic afferent (general sensory) – most lateral group – receives
sensations of pain, temperature, and touch from pharynx by way of
glossopharyngeal nerve
 Special afferent – intermediate group – receives impulses from taste
buds of tongue, palate, oropharynx, and epiglottis from
vestibulocochlear nerve for hearing and balance
 General visceral afferent – most medial group – receives interoceptive
information from GI tract and heart
 Roof plate of myelencephalon – consists of single layer of ependymal cells
covered by vascular mesenchyme (pia mater) – both layers together called tela
 Because of active proliferation of vascular mesenchyme, sac-like invaginations
called choroid plexus extend into underlying ventricular cavity and produce CSF
Metencephalon – characterized by basal and alar plates
 2 new components form cerebellum and pons
 Each basal plate of metencephalon contains
 Somatic efferent group – medial group that gives rise to nucleus of
abducens nerve
 Special visceral efferent group – containing nuclei of trigeminal and
facial nerves
 General visceral efferent group – axons that supply submandibular and
sublingual glands
Cerebellum formation
 Dorsolateral parts of alar plates bend medially to form rhombic lips
 In caudal portion of metencephalon, rhombic lips widely separated, but
immediately below mesencephalon, they approach each other in midline
 As a result of further deepening of pontine flexure, rhombic lips compress
cephalocaudally and form cerebellar plate
 12-week old embryo shows small cerebellar plate with
 Midline portion (vermis)
 2 lateral portions (hemispheres)
 Transverse fissure soon separates nodule from vermis and lateral flocculus from
 Floccularnodular lobe phylogenetically most primitive part of cerebellum
 Initially cerebellar plate consists of neuroepithelial, mantle, and marginal layers,
but during further development a number of cells formed by neuroepithelium
migrate to surface of cerebellum to form external granular layer
 Cells from this layer retain ability to divide and form proliferative zone
on surface of cerebellum
 During 6th month of development, external granular layer gives rise to various
cell types
Granule cells – formed from cells that migrate toward differentiating
Purkinje cells
 Basket and stellate cells – formed by proliferating cells in cerebellar whit
Cortex of cerebellum consists of Purkinje cells, Golgi II neurons, and neurons
produced by external granular layer – reaches its definitive size after birth
Deep cerebellar nuclei, such as dentate nucleus, reach final position before birth
o Each basal plate contains 2 groups of motor nuclei
 Somatic efferent group – medial group represented by oculomotor and
trochlear nerves that innervate eye musculature
 General visceral efferent group – represented by nucleus of Edinger-Westphal,
which innervates sphincter pupillary muscle
o Marginal layer of each basal plate enlarges and forms crus cerebri – these crura serve as
pathways for nerve fibers descending from cerebral cortex to lower centers in pons and
spinal cord
o Initially alar plates appear as 2 longitudinal elevations separated by shallow midline
depression – with further development, a transverse groove divides each elevation into
anterior and posterior colliculus
 Posterior colliculi serves as synaptic relay stations for auditory reflexes
 Anterior colliculi serves as correlation and reflex centers for visual impulses
 Both colliculi formed by waves of neuroblasts migrating into overlying marginal
zone where they are arranged in layers
Prosencephalon – consists of telencephalon (forms cerebral hemispheres) and diencephalon
(forms optic cup and stalk, pituitary, thalamus, hypothalamus, and epiphysis
o Diencephalon – develops from median portion of prosencephalon
 Consists of roof plate and 2 alar plates, but has no floor or basal plates
 Roof plate consists of single layer of ependymal cells covered by vascular
mesenchyme – give rise to choroid plexus of 3rd ventricle
 Most caudal part of roof plate develops into pineal body (epiphysis) –
initially appears in epithelial thickening in midline that begins to
invaginate by 7th week to eventually become solid organ on roof of
 Alar plates form lateral walls of diencephalon
 Hypothalamic sulcus – groove that divides plate into dorsal and ventral
region (thalamus and hypothalamus respectively)
 as result of proliferative activity, thalamus gradually projects into lumen of
diencephalon – frequently expansion so great that thalamic regions from right
and left sides fuse in midline, forming massa intermedia (interthalamic
hypothalamus differentiates into number of nuclear areas that regulate visceral
functions like sleep, digestion, body temperature, and emotional behavior
 mamillary body – group that forms distinct protuberance on ventral
surface of hypothalamus on each side of midline
 hypophysis (pituitary gland) – develops from ectodermal outpocketing of
stomodeum (primitive oral cavity immediately in front of oropharyngeal
membrane [Rathke’s pouch]) and a downward extension of diencephalon
 when embryo 3 weeks old, Rathke’s pouch appears as evagination of
oral cavity and subsequently grows dorsally toward infundibulum – by
end of 2nd month, it loses connection with oral cavity and is in close
contact with infundibulum
 cells in anterior wall of Rathke’s pouch increase rapidly in number and
form anterior lobe of hypophysis (adenohypophysis) – small extension
of this lobe (pars tuberalis) grows along stalk of infundibulum and
eventually surrounds it
 posterior wall of Rathke’s pouch develops into pars intermedia (not
much significance)
 occasionally, small portion of Rathke’s pouch persists in roof of pharynx
as pharyngeal hypophysis – craniopharyngiomas also arise from
remnants of Rathke’s pouch and may form within sella turcica or along
stalk of pituitary but usually above sella and may cause hydrocephalus
and pituitary dysfunction (diabetes insipidus, growth failure)
 infundibulum gives rise to stalk and pars nervosa (posterior lobe of hypophysis)
– composed of neuroglial cells and contains number of nerve fibers from
hypothalamic area
Telencephalon – most rostral of brain vesicles and consists of 2 lateral outpocketings
(cerebral hemispheres) and median portion (lamina terminales)
 Cavities of hemispheres (lateral ventricles) communicate with lumen of
diencephalon through interventricular foramina of Monro
 Cerebral hemispheres arise at beginning of 5th week as bilateral evaginations of
lateral wall of prosencephalon
 By middle of 2nd month, basal part of hemispheres (part that initially
formed forward extension of thalamus) begins to grow and bulges into
lumen of lateral ventricle into floor of foramen of Monro – called corpus
 In region where wall of hemisphere is attached to roof of diencephalon,
wall fails to develop neuroblasts and remains thin – consists of single
layer of ependymal cells covered by vascular mesenchyme (choroid
Choroid plexus protrudes into lateral ventricle along choroidal fissure as
a result of disproportionate growth of various parts of hemisphere
 Immediately above choroidal fissure, wall of hemisphere thickens,
forming hippocampus, which bulges into lateral ventricle and serves for
olfactory sensation
 With further expansion, hemispheres cover lateral aspect of
diencephalon, mesencephalon, and cephalic portion of metencephalon
 Corpus striatum also expands and is divided into two parts
o Caudate nucleus – dorsomedial portion
o Lentiform nucleus – ventrolateral portion
 Division of corpus striatum accomplished by axons passing to and from
cortex of hemisphere and breaking through nuclear mass of corpus
striatum – fiber bundle thus formed is internal capsule
 Medial wall of hemisphere and lateral wall of diencephalon fuse and
caudate nucleus and thalamus come into close contact
 Continuous growth of cerebral hemispheres in anterior, dorsal, and
inferior directions results in formation of frontal, temporal, and occipital
 As growth in region of corpus striatum slows, area between frontal and
temporal lobes becomes depressed (forms insula) and is later
overgrown by adjacent lobes (at time of birth, almost completely
 During final part of fetal life, surface of cerebral hemispheres grows so
rapidly that many convolutions (gyri) separated by fissures and sulci
appear on surface
Cortex develops from pallium and has 2 regions: paleopallium (also called
archipallium) immediately lateral to corpus striatum and neopallium between
hippocampus and paleopallium
 In neopallium, waves of neuroblasts migrate to subpial position and
differentiate into fully mature neurons – when next wave of neuroblasts
arrives, they migrate through earlier-formed layers of cells until they
reach subpial position – hence, early-formed neuroblasts obtain deep
position in cortex, while those formed later obtain more superficial
 At birth, cortex has stratified appearance due to differentiation of cells
in layers – motor cortex contains large number of pyramidal cells and
sensory areas characterized by granular cells
 Differentiation of olfactory system dependent on epithelialmesenchymal interactions that occur between neural crest cells and
ectoderm of frontonasal prominence to form olfactory placodes –
between these same crest cells and floor of telencephalon forms
olfactory bulbs
 Cells in nasal placodes differentiate into primary sensory neurons of
nasal epithelium, which has axons that grow and make contact with
secondary neurons in developing olfactory bulbs
o By 7th week, these contacts well established
 As growth of brain continues, olfactory bulbs and olfactory tracts of
secondary neurons lengthen and together constitute olfactory nerve
Commissures – in adult, number of fiber bundles that cross midline, connecting
right and left halves of hemispheres
 Most important fiber bundles make use of lamina terminalis
 First crossing bundles to appear is anterior commissure – consists of
fibers connecting olfactory bulb and related brain areas of one
hemisphere to those of opposite side
 Second commissure is hippocampal commissure (fornix commissure) –
fibers arise in hippocampus and converge on lamina terminalis close to
roof plate of diencephalon and continue forming arching system
immediately outside choroid fissure to mamillary body and
 Corpus callosum – most important commissure – appears by 10th week
of development and connects nonolfactory areas of right and left
cerebral cortices
o Initially forms small bundle in lamina terminalis, but as a result
of expansion of neopallium, extends first anteriorly and then
posteriorly, arching over thin roof of diencephalon
 Posterior and habenular commissures – just below and rostral to stalk of
pineal gland
 Optic chiasma – appears in rostral wall of diencephalon and contains
fibers from medial halves of retinae
CSF – secreted by choroid plexuses in brain ventricles – plexuses are
modifications of ependymal layer and produce approximately 400-500 mL of
CSF per day
 CSF circulates through brain ventricles, leaving lateral ventricles through
interventricular foramina, entering third ventricle, then passing through
cerebral aqueduct into 4th ventricle
 Some CSF enters spinal canal and some exits 4th ventricle through
median and lateral apertures to enter subarachnoid space that
surrounds CNS
 CSF absorbed into venous system from subarachnoid space thorugh
arachnoid granulations
Anterior neural ridge (ANR_ - at junction of cranial border of neural plate and nonneural
Isthmus – between hindbrain and midbrain
Cranial Defects
Schizencephaly –disorder where large clefts occur in cerebral hemispheres, sometimes causing
loss of brain tissue – caused by mutations in HOX gene EMX2
Ossification defects in bones of skull can result in meningoceles, meningoencephaloceles (part
of brain sticks out hole with meninges), and meningohydroencephaloceles (part of ventricle and
brain stick out with meninges) – most frequently affected bone is squamous part of occipital
bone, which may be partially or totally lacking
Exencephaly – characterized by failure of cephalic part of neural tube to close, and as a result,
vault of skull does not form, leaving malformed brain exposed – later this tissue degenerates,
leaving a mass of necrotic tissue – called anencephaly, even though brain stem remains intact
Craniorachischisis – closure defect of neural tube that extends caudally into spinal cord –
anencephaly occurs, but large defect involves spine
Because any anencephalic fetuses lack swallowing reflex, the last 2 months of pregnancy
characterized by polyhydramnios – more common in females than males – like spina bifida, can
be prevented by taking folic acid prior to and during pregnancy
Hydrocephalus – abnormal accumulation of CSF in ventricular system – in most cases, caused by
obstruction in aqueduct of Sylvius (aqueductal stenosis), which prevents CSF of lateral and 3rd
ventricles from passing into 4th ventricle and from there into subarachnoid space, where it
would be resorbed – as a results, fluid accumulates in lateral ventricles and presses on brain and
bones of skull – because cranial sutures have not yet fused, spaces between them widen as
head expands, resulting in large head and thin brain tissue and bone
Corpus callosum may be partially or completely absent without much functional disturbance
Leading cause of intellectual disability in fetuses is maternal alcohol abuse
Cranial Nerves
By 4th week of development, nuclei for all 12 cranial nerves present – all except olfactory and
optic nerves arise from brain stem and only oculomotor arises outside region of hindbrain
In hindbrain, proliferation centers in neuroepithelium establish eight distinct segments
(rhombomeres) that give rise to motor nuclei of cranial nerves IV-VII and IX-XII
Motor neurons for cranial nuclei are in brainstem, while sensory ganglia are outside brain
Cranial nerve sensory ganglia originate from ectodermal placodes and neural crest cells
o Ectodermal placodes include nasal, otic, and 4 epibranchial placodes represented by
ectodermal thickenings dorsal to pharyngeal (branchial) arches
o Epibranchial placodes contribute to ganglia for nerves of pharyngeal arches
o Parasympathetic ganglia derived from neural crest cells
Autonomic Nervous System
Sympathetic Nervous System
o In 5th week, cells originating in neural crest of thoracic region migrate on each side of
spinal cord toward region immediately behind dorsal aorta, where they form a bilateral
chain of segmentally arranged sympathetic ganglia interconnected by longitudinal nerve
fibers – together, they form sympathetic trunks on each side of vertebral column
o Neuroblasts migrate toward cervical and lumbosacral regions from thoracic origin,
extending sympathetic trunks to their full length
o Later, ganglia may become fused, particularly happens in cervical region
o Some sympathetic neuroblasts migrate in front of aorta to form preaortic ganglia, and
others migrate to heart, lungs, and GI tract, where they give rise to sympathetic organ
o Once trunks established, nerve fibers originating in visceroefferent column of
thoracolumbar segments of spinal cord penetrate ganglia of trunks
o Some of these fibers synapse at same levels in sympathetic trunks or pass through
trunks to preaortic or collateral ganglia
 Called preganglionic fibers – have myelin sheath and stimulate sympathetic
ganglion cells
 Passing from spinal nerves to sympathetic ganglia, they form white
communicating rami (only from T1-L2 or L3)
o Axons of sympathetic ganglion cells (postganglionic fibers) have no myelin sheath and
either pass to other levels of the sympathetic trunk or extend to the heart, lungs, and GI
o Gray communicating rami – pass from sympathetic trunk to spinal nerves and from
there to peripheral blood vessels, hair, and sweat glands – found at ALL levels of spinal
Suprarenal Gland – develops form 2 components: mesodermal portion that forms cortex and
ectodermal portion that forms medulla
o During 5th week, mesothelial cells between root of mesentery and developing gonad
begin to proliferate and penetrate underlying mesenchyme where they differentiate
into large acidophilic organs that form fetal cortex (primitive cortex) of suprarenal gland
o Shortly afterward, second wave of cells from mesothelium penetrates mesenchyme and
surrounds original acidophilic cell mass – smaller than cells of first wave and form
definitive cortex of gland
o After birth, fetal cortex regresses rapidly except outermost layer, which differentiates
into reticular zone
o Adult structure of cortex not achieved until puberty
o While fetal cortex forming, cells originating in sympathetic system (neural crest cells)
invade medial aspect, where they are arranged in cords and clusters – give rise to
medulla of suprarenal gland called chromaffin cells
During embryonic life, chromaffin cells scattered widely throughout embryo, but in
adult, only persisting group is in medulla of adrenal glands
Parasympathetic Nervous System
o Neurons in brainstem and sacral region of spinal cord give rise to preganglionic
parasympathetic fibers
o Postganglionic fibers arise from neurons (ganglia) derived from neural crest cells and
pass to structures they innervate
Congenital Megacolon
Also called Hirschsprung Disease
Results from failure of parasympathetic ganglia to form in wall of part or all of colon and rectum
because neural crest cells fail to migrate
Colon is dilated above affected region, which has small diameter because of tonic contraction of
noninnervated musculature
Ear Development
Internal Ear – first indication of developing ear around 22 days – starts as thickenings (otic
placodes) of surface ectoderm on each side of rhombencephalon – these invaginate rapidly to
form otic or auditory vesicles (otocysts) – during later development, each vesicle divides into a
ventral component that gives rise to saccule and cochlear duct as well as dorsal component that
forms utricle, semicircular canals, and endolymphatic duct (collectively membranous labyrinth)
o During 6th week of development, saccule forms tubular outpocketing at its lower pole
(cochlear duct) – cochlear duct penetrates surrounding mesenchyme in spiral fashion
until end of 8th week, when it has completed 2.5 turns
o Connection with remaining portion of saccule confined to narrow pathway called ductus
o Mesenchyme surrounding cochlear duct differentiates into cartilage
o In 10th week, cartilaginous shell undergoes vacuolization, and 2 perilymphatic spaces
(scala vestibule and scala tympani) are formed
o Cochlear duct is then separated from scala vestibule by vestibular membrane and from
scala tympani by basilar membrane
o Lateral wall of cochlear duct remains attached to surrounding cartilage by spiral
ligament – median angle connected to and partly supported by long cartilaginous
process (modiolus) which is the future axis of the cochlea
o Epithelial cells form 2 ridges: inner ridge (future spiral limbus) and outer ridge (forms
one row of inner and 3-4 rows of outer hair cells)
 Covered by tectorial membrane (fibrillar gelatinous substance attached to spiral
limbus that rests with tip on hair cells
 Sensory cells and tectorial membrane together form organ of Corti – impulses
received by this organ transmitted by spiral ganglion and then to nervous
During 6th week, semicircular canals appear as flattened outpocketings of utricular part
of otic vesicle – central portions of the walls of these eventually appose each other and
disappear, giving rise to 3 semicircular canals
 One end of each canal dilates to form crus ampullare and other end does not
widen and becomes crus nonampullare
o Cells in ampullae form crest (crista ampullaris) containing sensory cells for maintenance
of equilibrium
o Sensory areas (maculae acusticae) develop in walls of utricle and saccule
o During formation of otic vesicle, small group of cells breaks away from its wall and forms
statoacoustic ganglion – other cells of this ganglion derived from neural crest
 Ganglion splits into cochlear and vestibular portions, which supply sensory cells
of organ of Corti and those of saccule, utricle, and semicircular canals
Middle ear
o Tympanic cavity originates in endoderm and is derived from first pharyngeal pouch
 Pouch expands in lateral direction and comes in contact with floor of first
pharyngeal cleft
 Distal part of pouch (tubotympanic recess) widens and gives rise to primitive
tympanic cavity
 Proximal part remains narrow and forms auditory tube (Eustachian tube)
o Malleus and incus derived from cartilage of first pharyngeal arch, and stapes is derived
from that of second arch
 Ossicles appear during first half of fetal life, but remain embedded in
mesenchyme until 8th month, when surrounding tissue dissolves
 Endodermal epithelial lining of primitive tympanic cavity then extends along
wall of newly developing space
 When ossicles entirely free of surrounding mesenchyme, the endodermal
epithelium connects them in mesentery-like fashion to wall of cavity –
supporting ligaments of ossicles develop within these mesenteries
 During late fetal life, tympanic cavity expands dorsally by vacuolization of
surrounding tissue to form tympanic antrum – after birth, epithelium of
tympanic cavity invades bone of developing mastoid process and epitheliumlined air sacs are formed (pneumatization) – later, most of the mastoid air sacs
come in contact with the antrum and tympanic cavity
 Expansion of inflammations of middle ear into antrum and mastoid air cells is
common complication of middle ear infections
External Ear
o External auditory meatus – develops from dorsal portion of 1st pharyngeal cleft – at
beginning of 3rd month, epithelial cells at bottom of meatus proliferate, forming solid
epithelial plate (meatal plug) – in 7th month, the plug dissolves, and the epithelial lining
of the floor of the meatus participates in formation of definitive eardrum – occasionally
meatal plug persists until birth, resulting in congenital deafness
Eardrum is made of an ectodermal epithelial lining at bottom of auditory meatus, an
endodermal epithelial lining of tympanic cavity, and intermediate layer of connective
tissue that forms fibrous stratum
 Major part of eardrum firmly attached to handle of malleus and remaining
portion forms separation between external auditory meatus and tympanic
Auricle develops from 6 mesenchymal proliferations at dorsal ends of 1st and 2nd
pharyngeal arches – these swellings (auricular hillocks), 3 on each side of external
meatus, later fuse and form definitive auricle
 As fusion of auricular hillocks is complicated, developmental abnormalities of
auricle are common
Initially, external ears are in lower neck region, but with development of mandible, they
ascend to side of head
Hearing Loss and External Ear Abnormalities
Congenital hearing loss may be cause by abnormal development of membranous and bony
labyrinths or by malformations of auditory ossicles and eardrum
In most extreme cases, tympanic cavity and external meatus are absent
Rubella and cytomegalovirus infections during pregnancy can cause hearing loss
Isotretinoin (Accutane) can cause hearing loss in a child as well
External ear defects – common and often associated with psychological and emotional trauma,
especially since they are also often linked with other malformations
Preauricular appendages (skin tags) and pits (shallow depressions) – occur anterior to ear – pits
may indicate abnormal development of auricular hillocks – appendages may be caused by
accessory hillocks
Anotia – almost complete absence or complete absence of external ear
Microtia – small ear with abnormal features