Development Anat. Block B

• three expansions at rostral end of developing neural tube around 3 weeks of  development
• prosenscephalon: forebrain
• mesencephalon: midbrain
• rhombencephalon: hindbrain

• 5 differentiated enlargements of primary vesicles of the brain around 5 weeks of development
• prosencephalon becomes telencephalon and diencephalon
• mesencephalon continues on as mesencephalon
• rhombencephalon becomes metencephalon and myelencephalon

• walls form cerebral hemispheres, corpus striatum, & basal ganglion
• cavity becomes lateral ventricles

• walls form thalamus and surrounding area (hypothalamus, epithalamus, metathalamus, etc.) - leads to development of optic nerve
• cavity forms third ventricle

• continues on as midbrain
• cavity forms cerebral aqueduct (communication between 3rd & 4th ventricle)
• undergoes the least amount of differentiation

• walls become pons (origin of trigeminal nerve) and cerebellum (motor learning)
• cavity forms upper part of 4th ventricle

• walls form the medulla (continuous with spinal cord at foramen magnum just above spinal nerve C1)
• cavity forms lower part of 4th ventricle

midbrain + pons + medulla

• brain bends ventrally with formation of head folds
• formed during 4th week
• cervical flexure
• cephalic/mesencephalic/midbrain flexure
• pontine flexure

• level of foramen magnum (spinal nerve C1)
• NOT seen in adults
• between the rhombencephalon and hindbrain (myencephalon & spinal cord)

• AKA Cephalic/mesencephalic flexure
• between mesencephalon & prosencephalon
• Between axes of brainstem (vertical) & forebrain (horizontal)
• Seen in adult

• divides the hindbrain into myelencephalon (caudal) and metencephalon (rostral)
• causes reorganization of motor & sensory components
• causes neural tube walls to spread apart near 4th ventricle & thinning of the roof

• develops from thickenings in the dorsal parts of the alar plates
• cerebellar swellings enlarge & overgrow the rostral half of the 4th ventricle, the pons & the medulla
• forms cerebellum

• from myelencephalon
• pontine flexure causes neural tube to spread apart at 4th ventricle
• walls spread apart, roof thins out
• alar plates - lateral sensory components (GSA, GVA, SSA, SVA)
• basal plates - medial motor components (GSE, GVE, SVE)
• sulcus limitans divides alar & basal plates
• caudal portion of medulla is closed - central canal
• rostral portion is open in the region of metencephalon

• GSA
• GVA
• SSA: vision & hearing
• SVA: taste & olfaction
• GSE
• GVE
• SVE: motor component of muscles derived from pharyngeal arches

• cerebral hemispheres expand rapidly
• cover diencephalon, midbrain, and hindbrain
• floor of each cerebral hemisphere contains corpus striatum that expands more slowly than the cortical walls
• force C shaped telencephalon, lateral ventricles, internal capsule & corpus striatum
• grey matter on outside; white matter on inside

becomes dorsal horn of spinal cord segments

• derived from NCC
• central processes synapse on secondary sensory neurons in DRG

becomes ventral horn &  IMLCC

• surface of hemispheres is smooth
• initial development of telencephalon includes smooth surfaced cerebral hemispheres
• as development proceeds, sulci (grooves) and gyri (elevations) develop

allow considerable increase in surface area of the cerebral cortex without requiring extensive increase in cranial size

cerebral hemispheres in relatively confined space (skull) develop sulci & gyri to allow increased area of cerebral cortex & greater number of neurons without increasing brain size greatly

missing all or part of brain

• missing cerebral cortex
• due to failure in closure of anterior neuropore
• occurs in ~5/10000
• the brain is not formed
• the surrounding meninges & skull may be absent
• facial abnormalities may be present
• defect extends from level of lamina terminalis to foramen magnum
• neonatal death is inevitable
• lack of development of fetal cranial vault

• meroanencephaly
• anencephaly
• defects in ventral induction
• cerebral palsy
• cranium bifidum
• meningoencephalocele
• meningohydroencephalocele
• exencephaly
• hydrocephalus

• demarcates site of anterior neuropore closure
• visible on adult brain

• obstructive/noncommunicating hydrocephalus
• nonobstructive/communicating hydrocephalus

X linked genetic problem OR fetal viral infection (cytomegalovirus, toxoplasma gondii, etc.)

• cerebral aqueductal stenosis
• Physical obstruction of flow of CSF (produced in lateral 3rd ventricle & 4th ventricle)

• lateral aperature 
• CSF absorbed through arachnoid villi

• Problem with absorption of CSF through arachnoid villi to sagittal sinus
• Metabolic problem

• CSF produced in lateral ventricles, roots of 3rd & 4th ventricles
• flows out of ventricles into holes on caudal aspect of medulla
• foramen of Magenti: single midline communication between ventricular system & subarachnoid space
• foramne of Luschka: lateral aperatures (paired)
• CSF percolates through subarachnoid space
• CSF reabsorbed into sagittal sinus through arachnoid villi

• herniation of intracranial contents through a defect in the cranium
• cranium bifidum
• usually occur in the occipital region, but may occur in front or parietal locations
• meningocele: meninges only
• meningoencephalocele: meninges + brain
• meningohydroencephalocele: meninges + brain + part of ventricular system

• sequences of events by which the prosencephalon differentiates into the diencephalon & telencephalon
• normally - telencephalon divides into two cerebral hemispheres

• results from failure of cleavage of the prosencephalon into right & left cerebral hemispheres, telencephalon, & diencephalon
• little to no brain function
• associated with chromosomal anomalies (trisomy 13) and maternal diabetes mellitus

one big ventricular space

small cleft representing an attempt to separate the hemispheres

• sits in hypophyseal fossa
• functions in production of various hormones
• pars nervosa: anterior lobe
• pars tuberalis: posterior lobe

• neural ectoderm: diencephalon gives rise to diverticulum & pars nervosa
• superficial ectoderm: from roof of oral cavity (stomodeum); gives rise to pars tuberalis

evagination of dorsal aspect of stomodeum (roof of mouth) which meets the infundibulum of diencephalon

• closes off the oral cavity
• composed of superficial ectoderm & endoderm of the foregut
• under normal circumstances - gives rise to primitive stomodeum

• neuroectodermal origin
• leave the future brain well before closure of neural folds
• differentiate into mesenchyme in the head region
• migrate into pharyngeal arches
• participate in the formation of bones & CT of craniofacial structures

• endochondral bone formation
• membranous bone formation

• majority of bone forms this way
• mesenchymal cells first give rise to hyaline cartilage
• cartilagenous models become ossified

mesenchymal cells differentiate directly into bone

• develops from mesenchyme around the developing brain
• neurocranium: protective case for the brain
• viscerocranium: skeleton of the face/jaws

• membranous neurocranium: undergoes intramembranous bone formation; upper portion of skull
• cartilagenous neurocranium (chondrocranium): undergoes endochondral ossification; makes up base of skull

• begins in the 2nd month
• initially consists of cartilaginous base of the developing skull
• forms as fusion of several cartilages
• by the end of 3rd month, the base of the skull is a unified mass of cartilage
• endochondral ossification forms the bones of the base of the skull
• ossification commences before the chondrocranium has fully developed

• parachordal cartilage: base of occipital bone, foramen magnum
• hypophyseal cartilage: body of sphenoid bone
• trabeculae cranii: midline portions of the ethmoid bone
• orbitosphenoid: lesser wing of the sphenoid
• alisphenoid: greater wing of the sphenoid
• otic capsule: petrous & mastoid parts of the temporal bone
• nasal capsule: ethmoid, ethmoid air cells, inferior nasasl concha, nasal bone

• occipital bone: multiple ossification centers
• petromastoid temporal bone: multiple ossification centers
• sphenoid bone: >16 ossification centers
• ethmoid bone: 3 ossification centers
• inferior nasal concha: 1 ossification center
• nasal bone: 1 ossification center

• present between bones and/or ossification centers before bones fuse together
• analagous to epiphyseal plates
• cartilaginous joints
• union of two bones separated by hyaline cartilage
• most common type of joint in developing bone
• bony epiphysis + body are united by epiphyseal cartilage

• frontal
• parietal
• squamous occipital
• squamous temporal
• lacrimal

• induced by specifica parts of the developing brain
• intramembranous ossification occurs in the mesenchyme at sides & top of the brain forming the calvaria

dense connective tissue that separates the flat bones of the calvaria

• anterior
• posterior
• mastoid/ posterolateral (2)
• sphenoid/anterolateral (2)

• largest fontanelle
• at the junction of sagittal, coronal & frontal sutures
• closes at the middle in 2nd yr of life

• posterior & lateral fontanelles: 1-2 months
• anterior: 2nd year

• continuous with frontal suture
• may not close in oriental individuals

• determines progress of growth in surrounding bones
• determines degree of hydration of baby (if dehydrated, fontanelles will be depressed)
• determines state of intracranial pressure

• cartilages of the first two pharyngeal arches
• 1st pharyngeal arch, dorsal end: malleus + incus
• 2nd pharyngeal arch, dorsal end: stapes + styloid process
• 2nd pharyngeal arch, ventral end: lesser horn & upper body of hyoid bone
• 3rd pharyngeal arch: greater horn & lower body of hyoid bone

• intramembranous ossification occurs in the maxillary prominence
• maxillary bone
• zygomatic bone
• palatine bone
• vomer
• pterygoid laminae
• nasal bone

mesenchyme in the mandibular prominence of the 1st arch condenses around its Meckel's cartilage and undergoes intramembranous ossification

• large in proportion to other parts of the skeleton
• facial portion of cranium is small (equals 1/8 the bulk of the skull in the new born, 1/2 the bulk in adults)
• nasal cavities lie almost entirely between the orbits
• lower border of anterior nasal aperture is only a little below the level of the orbital floor
• mastoid process is not developed - facial nerve is close to surface and may be damaged by forceps

• rudimentary condition of maxilla & mandible
• non-eruption of the teeth
• small size of the maxillary air sinuses and nasal cavities

• fibrous sutures permit skull to enlarge during infancy & childhood
• skull rapidly grows from birth to 7th year
• calvaria normally increases in capacity until 15-16 years of age
• after 16 yrs, the calvaria usually increases in size for 3-4 years because of thickening of bone

• sagittal suture: 22 yrs
• sphenofrontal suture: 22 yrs
• coronal suture: 24 yrs
• lambdoidal suture: 26 yrs
• occipito-mastoid suture: 26 yrs
• sphenoparietal suture: 29 yrs
• sphenotemporal suture: 30 yrs
• parietomastoid suture: 37 yrs
• squamous suture: 37 yrs

• account for 1/3 of skull malformations
• most are multifactorial
• stem from interaction of environment or outside influences with individual's own genetic determinants
• individuals show different susceptibilities to the actions of a given teratogen

• alchohol
• toluene
• smoking
• hyperthermia
• hydantoin
• accutane
• ionizing radiation

• acrania/anencephaly: congenital defective development of the brain with absence of bones of the cranial vault
• microcephaly: size of cranial vault accomodates to very small brain
• hydrocephaly: greatly enlarged cranial vault that represents excessive build up of CSF

• congenital anomaly characterized by premature closure of skull sutures
• pathogenesis unknown - probably genetic
• may result from environmental insults (trauma, drugs, intrauterine infections)

• fusion of suture present at brth (defect occurred in utero)
• lack of growth of skull perpendicular to affected suture
• overgrowth of skull parallel to affected suture

• abnormality centered in skull base
• skull base deformity (especially in sphenoid) results in premature fusion of calcified structures due to transmission of abnormal forces from skull base through the dura to sutures themselves
• calvarial sutures fuse prematurely & skull bone deformities occurred secondarily
• abnormality centered in mesenchymal cells of embryo - affected both calvarial & basilar structures
• fetal head constraint: premature descent of fetus into pelvis

• results from failure of brain growth & expansion
• sickle cell anemia: inherited disorder of hemoglobin metabolism
• hyperthyroidism: low CSF pressure caused by ventricular-peritoneal shunt

• scaphocephaly: sagittal suture fused; boat skull
• trigonocephaly: metopic suture fused; triangular skull
• plagiocephaly: unilateral coronal suture fused; asymmetric skull
• brachycephaly: bilateral coronal suture fused; short skull
• plagiocephaly: lambdoid suture fused; asymmetric skull

• most frequent non-syndromic craniosynostosis
• occurs more commonly in males
• sagittal suture closes prematurely
• compensatory anteroposterior growth
• skull becomes narrow & wedge shaped - boat skull du to frontal & occipital bossing

• Saethre-Chotzen Syndrome
• Crouzon Syndrome
• Apert Syndrome
• Pfeiffer Syndrome

• neuroectoderm + neural crest cells
• superficial ectoderm
• mesenchymal mesoderm

• at 22 days, cranial end of neural tube is still open
• invagination of neural folds
• becomes evagination of rostral part of brain with closure of neural folds

• original cavity of the optic vesicles (from prosencephalon)
• associated with diencephalon (division of prosencephalon)
• becomes intraretinal space

originates from the more proximal part of the optic vesicle due to differential growth between the prosencephalon & the optic vesicle

optic vesicle/ opticoele induces superficial ectoderm to thicken and form the lens placode

invagination of central region of lens placode

superficial ectoderm cause invagination of optic vesicle (opticoele I)

• cavity of optic cup
• formed by invagination of optic vesicle

• outer/proximal wall: becomes pigmented layer of retina
• inner/distal wall: forms sensory layer of retina

• AKA retinal or optic fissure
• groove formed along the ventral part of the optic cup
• extends back along the optic stalk
• contains the hyaloid artery & vein
• directing pathway for axons of ganglion cells of the retina that will eventually form the optic nerve

formed from proximal parts of hyaloid artery within choroid fissure

• distal parts of hyaloid artery & vein degenerate
• pieces may break off and occlude vision temporarily

most likely to occur at intraretinal space (originally opticoele I) if layers of optic cup are not tightly fused

• frontal wall of lens vesicle remains cuboidal - become lens epithelium
• epithelial cells produce an elastic, non cellular lens capsule
• back wall differentiates into tall columnar cells which lose their nuclei, become transparent - become lens fibers
• lens fibers continually produced at the equator

• thicker portion of optic cup; back 4/5 of cup
• forms photosensitive retina
• outer layer - pigmented layer of retina (RPE)
• inner layer - sensory layer of retina

• anterior 1/5 of optic cup that remains thin
• forms non-photosensitive retina
• pars iridica: forms iris
• pars ciliaris: forms ciliary body & processes

point of junction between pars optica and pars caeca of optic cup

• part of pars caeca (nonphotosensitive retina) from optic cup
• becomes iris
• pupillary membrane undergoes apoptosis to expose pupil
• dilator & constrictor pupillae muscles derive from pars iridica (neuroectoderm of outer layer of optic cup)
• stroma of iris develops from mesenchyme

• part of pars caeca (nonphotosensitive retina) from optic cup
• becomes ciliary body & processes
• ciliary muscle derives from mesenchyme
• choroid derives from mesenchyme adjacent to the optic cup (becomes pigmented & vascular)
• sclera derives from superficial mesenchyme

• substantia propria: develops from mesenchyme between superficial ectoderm & optic cup in front of developing eye
• corneal epithelium: develops from superficial ectoderm
• conjunctiva: develops from superficial ectoderm

• from superficial ectoderm + mesoderm
• start as folds
• fuse around 10 weeks
• separate again around 26 weeks

• failure of iridopupillary membrane to undergo apoptosis within pars iridica
• congenital atresia of the pupil: trabeculae across pupil
• Rx - laser removal

• genetic defect
• may result from maternal Rubella
• incomplete formation of canals of Schlemm or spaces of Fontana/trabecular meshwork

• Excessive tearing
• Sensitivity to light (photophobia)
• Large appearing eye (excessive fluid)
• Cloudiness of eyes
• May result in blindness

may result from maternal Rubella

• abnormal cleft in either eyelid (palpebral) or iris (iridis)
• may be genetic or environmental

• pupil has keyhole appearance
• results from failure of choroid fissure to close properly

• Eyes are partially or completely fused into a single median eye
• Tubular nose or proboscis is above eye
• Autosomal recessive
• ex. Trisomy 13 - Patau syndrome

• failure of development of the levator palpebrae superioris muscle
• may result for incomplete innervation of muscle
• hereditary

• absence of eyeball
• results from the failure of the optic vesicle to form

• arrested development of the optic vesicle
• genetic: recessive or sex linked
• environmental: Rubella, Herpes simplex, Toxoplasma gondii viruses

failure of layers to fuse due to unequal growth of optic cup

• congenital absence of lens
• results from failure of lens placode to form OR degeneration of the lens during fetal development

failure of eyelids to form

• condesations of mesodermal mesenchyme and neural crest cell mesenchyme
• transverse swellings of mesenchyme that flank the foregut
• contribute to the formation of the face, nasal cavities, mouth, larynx, & neck
• originally have core of mesodermal mesenchyme
• NCCs migrate into pharyngeal arches

diverticulum of the endoderm from foregut

invaginations of the superficial ectoderm towards the pharyngeal pouches

combination of endoderm of pouch wth ectoderm of grooves

• pharyngeal arches
• pharyngeal pouches
• pharyngeal grooves
• pharyngeal membrane

• 23 days: first signs of pharyngeal arches
• 24 days: 1st and 2nd arches visible with 1st pharyngeal groove
• 26 days: 3rd arch is visible
• 28 days: 4th arch visible (4 weeks = 4 arches)
• 5th & 6th arches are rudimentary

• surrounded by first arch
• ruptures via apoptosis
• becomes oral cavity (stomodeum)

• aortic arch - from truncus arteriosus
• cartilagenous rod
• muscular component
• nerve - from primordial brain

mesodermal mesenchyme

• bone
• dentin
• cartilage
• pigment cells
• glandular stroma - thyroid (C cells); parathyroid; thymus; salivary glands

• neuroectodermal origin
• leave the future brain well before closure of the neural folds
• differentiate into mesenchyme in the head region
• participate in the formation of bones & CT of craniofacial structures

• trunk neural crest: Hirschsprung's disease (aganglionic colon)
• cranial neural crest: aorticopulmonary septation defects of heart; anterior chamber defects of eye; cleft lip and/or palate; frontonasal dysplasia; DiGeorge syndrome; dental anomalies
• trunk & cranial neural crest: CHARGE syndrome; Waardenburg syndrome

• coloboma: failure of choroid fissure to close
• heart defects: tetralogy of Fallot
• atresi choanae: blocking of airway, cannot breath through nose
• retardation of growth & development: sensory deficits, mental retardation
• genitourinary problems: genital hypoplasia, undescended testes, small labia
• ear abnormalities: unusually shaped ears, sensory or conductive hearing loss

• autosomal dominant
• defect in migration of neural crest cells
• family history of parent with Waardenburg syndrome
• extremely pale blue eyes or heterochromia
• partial albinism - white forelock (poliosis) of hair; early greying of hair
• deafness (variable degree)

• pherochromocytoma: tumor or chromaffin tissue of adrenal medulla
• neuroblastoma: tumor of adrenal medulla and/or autonomic ganglia
• medullary carcinoma of thyroid: tumor of parafollicular (calcitonin secreting) cells of the thyroid
• carcinoid tumors: tumors of enterochromaffin cells of digestive tract
• neurofibromatosis: von Recklinghausen; peripheral nerve disease

• neural crest cell defects
• lack of RPE allows visualization of choriovessels

• 2nd pharyngeal arch enlarges and overgrows the 3th & 4th arches
• disappears by end of 7th week (2nd and 4th grooves disappear) to give neck a smooth appearance

• dorsal end: malleus & incus
• middle part: regresses; perichondrium forms anterior ligament of malleus & sphenomandibular ligament
• ventral part: primordium of mandible

• first pharyngeal arch
• plays a major role in facial development
• maxillary prominence & mandibular prominence produced by migration of neural crest cells into the first arch

• maxilla
• zygomatic arch
• squamous portion of temporal bone

sets up precursor of Meckel's cartilage (primordium of mandible)

gives rise to the nose

invaginates to lead to oropharyngeal membrane (composed of foregut & superficial ectoderm of stomodeum)

superior evagination of the ventral diverticulum of the foregut at the level of the 2nd pharyngeal pouch

• dorsal end: stapes; styloid process of temporal bone; stylohyoid ligament (from intermediate perichondrium)
• ventral part: lesser cornu & superior part of body of hyoid bone

first arch cartilage

second arch cartilage

• greater cornu
• inferior part of body of hyoid

• laryngeal cartilages (except epiglottis)
• epiglotic cartilage forms from the mesenchyme in the hypopharyngeal eminence

arch is rudimentary - NO derivatives

• muscles of mastication - temporalis, lateral and medial pterygoids, masseter
• tensor veli palatini
• tensor tympani
• anterior belly of digastric
• mylohyoid

• stapedius
• stylohyoid
• posterior belly of the digastric
• all muscles of facial expression (including buccinator and auricular muscles)

stylopharyngeus

• cricothyroid
• levator veli palatini
• constrictors of the pharynx

intrinsic muscles of the larynx

• each pharyngeal arch is associated by its own cranial nerve
• each nerve supplies the muscles derived from its associated pharyngeal arch muscle
• each nerve supplies the dermis & mucous membranes derived from its associated pharyngeal arch

• lateral aspect: tubotympanic recess; tympanic cavity & mastoid antrum
• proximal portion: pharyngotympanic tube
• membrane: tympanic membrane

tonsillar sinus/fossa (mostly obliterated by palatine tonsil)

• dorsal: inferior parathyroid gland
• ventral: thymus

• superior parathyroid gland
• with remnants of 5th pouch - ultimopharyngeal body (parafollicular or C cells of thyroid)

• fistulas
• sinuses
• cytes
• ectopic glands or glandular tissue

• located near the external auditory canal
• commonly inferior & posterior to the tragus (base of ear)
• may also be in the parotid gland or angle of mandible
• may be difficult to distinguish from a solid parotid mass on clinical examination

associated with submandibular gland or found in the anterior triangle of the neck

• accounts for 95% of branchial anomalies
• congenital cyts that arise in the lateral aspect of the neck when the second branchial cleft fails to close during embryonic development
• cysts are identified along the anterior border of the upper third of the SCM (adjacent to the muscle)
• may present anywhere along the course of the lateral neck between the internal & external carotid arteries and into the palatine tonsil

• RARE
• extends from lateral neck posterior to the carotid arteries and pierces the thyrohyoid membrane to enter the larynx
• usually located deep to the SCM
• sometimes mistaken for retropharyngeal abscesses

• RARE
• arise from lateral neck, parallel to course of recurrent laryngeal nerve (around aorta on the left and around the right subclavian artery)
• terminate in pyriform sinus
• may arise in mediastinum

• usually located in area of skin anterior to auricle
• classified as minor anomalies - no serious medical consequence

• incomplete closure of cervical sinus
• can appear anywhere along SCM
• courses in between internal & external carotid arteries

• results from insufficient migration of neural crest cells into the first arch during the fourth week
• treacher collins syndrome: main manifestation

• mandibulofacial dysostosis
• autosomal dominant gene
• malar hypoplasia
• downslanting palpebral fissures
• defects of the lower lids
• deformed external ears
• abnormalities of middle & internal ears

• ventral endodermal thickening in floor of pharynx (thyroid diverticulum) at level of 2nd pharyngeal pouch
• thyroglossal duct opens at foramen cecum of tongue
• thyroglossal duct courses anterior to hyoid bone until it reaches tracheal cartilage due to differential growth

• can occure anywhere along the course followed by the thryoglossal duct during descent of the primordial thryoid gland from the tongue
• painless, progressively enlarging movable mass
• with infection, perforation of the skin occurs (thyroglossal duct sinus)

• lingual thyroid tissue
• sublingual thyroid gland
• substernal thryoid gland

• hot potato speech
• difficulty in breathing & swallowing
• four times more common in females than in males
• cannot remove if it is the only thyroid tissue available

• ectopic thyroid tissue
• stays high in neck

• ectopic thyroid tissue
• migrates too far in the mediastinum

median tongue bud (tuberculum impar)

• END OF 4th WEEK
• median lingual swelling (tuberculum impar): disappears and makes no contribution to the adult tongue
• median sulcus: point of fusion of two distal tongue buds
• lateral lingual swelling: overgrow median lingual swelling to form anterior 2/3 of tongue
• posterior 1/3 of tongue: from rostral part of hypopharyngeal eminence (3rd & 4th arches)
• tongue musculature: from occipital myotomes

• ankyloglossia: tongue-tie
• macroglossia: large tongue
• microglossia: small tongue
• bifid tongue: split tongue

• tongue-tie
• short frenum - extends to tip of tongue
• inferferes with protrusion of tongue
• may make breastfeeding difficult