Embryology Flashcards
Notochord role in neural development?
notochord induces overlying ectoderm to differentiate into neuroectoderm and form the neural plate → edges elevate to form folds and depresses for groove → fusion at 5th somite ~week 4
What does the neural plate give rise to?
neural tube (brain and spinal cord) and neural crest cells.
Neural crest: PNS, ganglia, schwann cells, melanocytes, satellite cells, arachnoid & pia mater, merkel cells (pressure), cartilages of head and neck
What does the notochord become in adults?
the nucleus pulpous of the intervertebral disc
Alar vs basal plate?
Within intermediate layer (gray matter of spinal cord) neuroblasts develop into alar/basal separated by sulcus limitans
- Alar (dorsal) = sensory (2° afferent dorsal horn)
- Basal (ventral) = motor (efferent ventral horn, preganglionic sympathetic neurons)
Cell layers in neural tube?
Ventricular: neuroepithelial neural canal → ependyma
Intermediate: neuroblasts (gray matter)→ alar/basal
Marginal: axons of neuroblasts (white matter)
Three primary vesicles of developing brain?
Prosencephalon
telencephalon: Lateral ventricle
Cerebrum, insula, basal ganglia, corpus collosum, internal capsule, CN I
diencephalon: 3rd ventricle
thalamus, hypo-, epi-, CNII and retina, posterior pituitary, infundibulum
Mesencephalon
mesencephalon: midbrain, cerebral aqueduct
Rhombencephalon
metencephalon: pons, cerebellum, 4th ventricle
myelencephalon: medulla
What does the neuroectoderm give rise to?
CNS neurons; ependymal cells (inner lining of ventricles, make CSF); oligodendroglia; astrocytes.
What does neural crest give rise to?
PNS neurons, Schwann cells (peripheral myelination)
What does mesoderm give rise to?
Microglia (Macrophages, originate from Mesoderm)
Neural tube defects
Neuropores fail to fuse (4th week)→ persistent connection between amniotic cavity and spinal canal.
Low Folic Acid before and during pregnancy
Elevated alpha-fetoprotein (AFP)
Increased acetylcholinesterase (AChE)
Spina Bifida (neural tube defect)
Failure of caudal neuropore to close→bony spinal canal doesn’t close.
- Occulta: No herniation, dura intact, associated with faun tuft of hair or dimple at defect level
- Meningocele: meninges bulge with CSF. Normal AFP
- Meningomyelocele: meninges and cord herniate.
Anencephaly (forebrain anomaly)
Malformation of anterior neural tube= no forebrain, open calvarium.
“frog-like” appearance
Clinically: incr AFP; polyhydramnios (no swallowing center).
Associated w/ maternal DM type 1
Maternal folate supplementation decr risk.
Holoprosencephaly (forebrain anomaly)
Failure of Lt and Rt hemispheres to separate; usually during weeks 5-6. May be related to mutation in sonic hedgehog signaling.
Clinically: moderate form has cleft lip/palate, severe form results in cyclopia.
Arnold-Chiari posterior fossa malformation (Chiari II)
Herniation of cerebellar tonsils and vermios through foramen magnum w/ aqueductal stenosis and hydrocephalus.
Often presents w/ myelomeningocele and paralysis.
Dandy-Walker (posterior fossa malformation)
Agenesis of cerebellar vermis w/ cystic enlargement of 4th ventricle (fills the enlarged posterior fossa).
Associated w/ hydrocephalus and spina bifida.
What do the 1st and 2nd branchial arches form?
Anterior 2/3 of tongue
(sensation via CN V3, taste via CN VII)
What do the 3rd and 4th branchial arches form?
Posterior 1/3 of tongue
(sensation and taste mainly via CN IX, extreme posterior CN X)
What are the musculoskeletal and neural derivatives of each pharyngeal arch?
1st: CN V3, malleus, incus, mylohoid, ant belly digastric
“muscles of mastication”
2nd: CN VII, stapes, stapedius,stylohoid, post belly digastric, “muscles of facial expression”
3rd: CN IX, stylopharyngeus
4th: CN X (superior laryngeal), soft palate, pharynx
6th: CN X (recurrent), larynx and exophagus
Choanal Atresia?
Improper opening of choanae due to failure of apoptosis of oronasal membrane.
“My newborn is having difficulty breathing and can’t breastfeed”
“My daughter’s nose is always running; she cannot breathe through it.”
Anterior lip and palate defects
Failure of fusion of maxillary prominences with the fused medial nasal prominences.
1 in 1000 births and 60-80% males increasing with increasing maternal age.
Posterior palate defects
Failure of fusion of the palatine shelves with one another with the nasal septum and with the posterior margin of the primary palate.
Involves hard and soft palate.
1 in 2,500 births, 2x as common in girls. No link to maternal age.
Wide variation: all of hard and soft palate, only soft palate, only uvula (bifid); unilateral of bilateral.
Fetal Alcohol Syndrome (FAS)
Characteristic facial features: flat face, small palpebral fissures, small jaws
Predominantly neurological features (only 4-6% show physical signs).
1st trimester: interferes w/ migration, organization
2nd: difinitive FAS traits
3rd: hippocampus, problems w/ math, reading
Congenital coloboma
Defective closure of the choroid or optic fissure.
Positioned in the inferonasal quadrant, relective of the location of the optic fissure during fetal development.
External Ear Malformation
Failure of 1st cleft to invaginate.
part of several syndromes: first arch syndromes, chromosomal abnormalities.
Present as:
- Auricular appendages/tags from excess hillock mesenchyme
- Auricular cysts (fistulas) from incomplete fusion of hillocks
- Microtia: abnl shape or size of ear, varies in severity.
- Anotia: agenesis, inner may be normal.
Congenital Neurosensory Deafness
Abnormal development of cochlea, CN VIII, or brainstem
Causes:
- Rubella in 1st trimester→defects in organ of corti in 30% of cases
- Neural crest defect→migratory melanocytes from NC don’t properly form stria vascularis
Congenital conduction deafness
Persistence of meatal plug (1st arch syndrome)
- Fixation of footplate of stapes
- Abnormalities of malleus and incus often
Microopthalmia
Arrested development of optic vesicle; globe is small, lens doesn’t form
Anopthalmia
Arrested development of optic vesicle early in 4th week, usually accompanies severe craniocerebral defects.
Congenital Glaucoma
Cloudy cornea from abnormally high intraocular pressure, usually from malformed drainage apparatus.
Genetic abnormalities account for 85% of cases, also Rubella.
Cupping on eye exam.
Persistent hyaloid artery of pupillary membrane
Failure of either to dissolve in development.
Hyaloid artery: normal regression ~11 weeks and completely gone by 8 months.
Pupillary membrane: may interfere w/ visual acuity.
CHARGE syndrome
Coloboma
Heart defects
Atresia of choanae
Retarded growth/development
Genital hypoplasia
Ear abnormalities
Congenital Ptosis
Does not affect vision, correctable via surgery by tightening LPS
Autosomal dominant
Result from birth trauma, myasthenia gravis, abnl CNIII development, or dysgenesis of LPS.
Nasolacrimal groove atresia
Results in canalization failure, infection is common, and newborn may have constant tearing/mucuous drainage, and subsequent chapping of periocular skin.
Microtia
Grade 1: Ear slightly smaller than nl; no surg needed
Grade 2: Auricle half-size; surgery beneficial
Grade 3: Small cartilage present; repair at age 5-6
Lop ear
Most common external ear abnormality; absence of antihelical fold, cosmetic surgery offered.
Prequricular pits and fistulas
Frequently infected pits in front of ear
Tx: w/ antibiotics and incision and drainage
Auricular appendages
Arrested development of fusion of the hillocks of His. Growth that contains cartilage and skin.
Tx: elective excision
Derivatives of 1st-4th pharyngeal pouches?
1st: Auditory tube, mastoid air cells
2nd: Palatine tonsils
3rd: Thymus and inferior parathyroid
4th: Thyroid and superior parathyroid
First Arch Syndrome?
Treacher Collins Syndrome:
-fishmouth appearance, midface deformity, thin lower face, small jaw
Pierre Robin Syndrome:
-cleft palate, posterior displaced tongue, micrognathia. -Tx: tracheostomy, mandible lengthening hardware
DiGeorge syndrome?
No thymus or parathyroids (3rd and 4th pouch)
Low immunity and hypocalcemia
Ectopic thyroid, parathyroid or thymus
Accessory or ectopic parathyroid are highly variable in number and location. Inferior may fail to descend, remain near bifurcation of carotic artery. May be found in thorax w/ thymus.
Accessory thymus tissue: portions of the tail may break off and found in the thyroid, in association w/ the inferior parathyroid or in isolated “nests”
Lateral cervical cyst and fistula
Branchail cleft, 2nd arch most common
Lump located along the anterior border of SCM muscle, below angle of the mandible.
Due to incomplete overgrowth of the 2nd, 3rd, 4th clefts by the 2nd arch.
Thyroglossal duct cyst of fistula
Remnant of thyroglossal duct
Midline - usually near hyoid, but may be from the base of the tongue down to thyroid cartilage.
May be associated w/ URI sxs.
Ankyloglossia
Lingual phrenulum still attached, can’t breast feed.
Congenital megacolon or Hirschsprung’s disease?
Neural crest cells fail to migrate into colon; parasympathetic gangli do not form → no peristalsis
Usually sigmoid colon and rectum, fecal retention
Waardenburg syndrome?
Diffuse disruption of neural crest cell migration.
Abnormal face appearance, deafness,
lack of pigmentation (melanocytes),
digestive problems (enteric ganglia)
Cranial Malformations
due to craniosynostosis; premature closure of sutures
- Scaphocephaly: sagittal sutures = long narrow head
- Oxycephaly: coronal and lambdoidal sutures; tower
- Brachycephaly: bilat coronal suture; wide skull
- Plagiocephaly: unilateral coronal or lambdoidal
- Trigonocephaly: frontal (metopic); pointy forehead
Deformational Plagiocephaly: positional malformations from laying on back, may require different sleeping postion or helmet.
Apert Syndrome
Autosomal dominant; mutation in fibroblast growth factor receptor 2 gene.
Sx: under developed face, symmetric syndactyly, hearing loss/freq infection, short stature, slow
Cruzon synd: similar to Apert but only craniofacial.
Microcephaly
small head, usually due to underdeveloped brain. Mentally deficient. May be genetic or due to radiation exposure, infectious agents, drugs/EtOH, rubella, or chicken pox
Cranioschisis
Cranial vault fails to close due to failure of cranial neuropore to close usually in occipital region.
(similar to spina bifida in the posterior head)
Hydrocephalus
Build-up of CSF in brain →ventricle enlargement →pressure on cortex →brain damage
1 in 1000 live births
Neurocranium vs viscerocranium
Neurocranium: develops around rostral end of the neural tube, gives rise to bones surrounding brain and special sense organs.
Viscerocranium: develops around the gut tube, gives rise to lower face, jaws, palate, larynx, hyoid, epiglottis.
Facial Primordia (week 4)
- 5 facial prominences(neural crest→pharyngeal arch)
a. frontanasal: mesenchyme ventral-brain vesicles
b. maxillary(2): extension from 1st pharyngeal arch
c. mandibular(2): mesenchyme 1st pharyngeal arch - Placodes (ectodermal thickenings→special sense)
a. lens placode: lens
b. otic placodes: inner ear
c. nasal placodes: nasal cavity and part upper lip - Stomodeum(ectoderm depression→future mouth site
Palate formation
forms between weeks 5-12 (critical 6-9)
Primary palate from intermaxillary segment.
Secondary palate from palatine processes of maxillary prominences growin medially; fuse anterior to posterior (uvula region fuse ~12 weeks)
Primary/Secondary fusion = incisive foramen
Hard palate (primary palate + rostral 2° palate = intramembranous bone) forms from maxilla and palatine bones.
Congenital cataracts
cloudy or opaque lens. May be inherited, caused by rubella virus or congenital galactosemia.
Coloboma
Failure of optic fussure to close, may leave gap anywhere along it’s path.
Anterior coloboma (of iris) presents as a key-shaped pupil, usually in inferior nasal quadrant. vision may be normal. retinal or optic nerve proximal defects produce large deficits in visual field.
Detached Retina
RPE is adhered to choroid but neural and RPE layers not adhered to one another. Poor fusion in development. May be co-morbid with Marfan or Down synd.
