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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 hemispheres) o Diencephalon – characterized by outgrowth of optic vesicles Rhombencephalic isthmus – deep furrow that separates mesencephalon from rhombencephalon 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 o 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 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 o o 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 choroidea 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 hemispheres 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 ematter 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 Mesencephalon 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 mesencephalon 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 connexus) o 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 (infundibulum) 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 striatum 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 plexus) 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 lobes 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 covered) 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 position 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 hypothalamus 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 ectoderm 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 plexuses 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 tract 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 cord 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 o 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 reuniens 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 system o 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 o o o 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 cavity 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