Lecture 2

What is the major outcome of gastrulation?

Formation of the three germ layers (ectoderm, mesoderm, endoderm) from the bilaminar embryo

What are somatic cells derived from?

The three embryonic germ layers established during gastrulation

What do epiblast cells passing through the primitive streak first displace, and what does this form?

They displace the hypoblast, giving rise to the embryonic/definitive endoderm

What do cells at the primitive node give rise to as the streak regresses?

Head mesoderm and the notochord

What forms the embryonic mesoderm?

Cells moving through the primitive streak between the epiblast and endoderm

What becomes of epiblast cells that remain at the surface?

They form the embryonic ectoderm

What does the oropharyngeal membrane become?

The stomodeum (mouth opening)

What does the cloacal membrane become?

The opening of the anus

Where is the oropharyngeal membrane located?

At the cranial end of the embryo

Where is the cloacal membrane located?

At the caudal end of the embryo

Name the three major derivatives of the ectoderm

Epidermis, central nervous system, neural crest derivatives

Name four cranial placode derivatives

Inner ear, lens, olfactory epithelium, cranial ganglia

What is neural induction?

The process by which the neural plate is generated via inductive interaction between the chordamesoderm/notochord and the ectoderm

What secreted molecule regulates the decision between epidermal and neural fate in the ectoderm?

Bone morphogenetic protein 4 (BMP4)

What must happen to BMP4 signaling to convert ectoderm into neural tissue?

It must be inhibited

What three molecules act as BMP4/BMP antagonists?

Noggin, Chordin, and Follistatin

Where are Noggin, Chordin, and Follistatin secreted from?

The dorsal mesoderm/notochord

What character (anterior/posterior) is the nervous tissue induced by BMP4 inhibition alone?

Anterior in character (forebrain type)

What three signals transform anterior neural tissue into posterior (hindbrain/spinal cord) tissue?

FGF, Wnt-3a, and Retinoic acid

What is neurulation?

The process by which the neural plate folds into the neural tube

What are the ectoderm derivatives segregated during neurulation?

Neural tube, neural crest, epidermis

List the five stages of neural tube formation in order

Shaping, folding, elevation, convergence, closure

Where does neural tube closure begin, and how does it proceed?

It begins at the level of the future midbrain and "zips up" in both directions

What are the last regions of the neural tube to close called?

The cranial and caudal neuropores

What is anencephaly?

Failure to close the anterior part of the neural tube

What is spina bifida?

Failure to close the neural tube in the caudal region

What determines the severity of spina bifida?

How much of the spinal cord is exposed through the vertebral arches and other superficial structures

What two structures act as organizing centers for dorsoventral patterning of the spinal cord?

The notochord and the floor plate

What molecule acts as a morphogen to generate neuronal diversity in the ventral spinal cord?

Sonic hedgehog (Shh)

What does a high concentration of Shh (closest to the notochord/floor plate) induce?

Motor neurons (ventral-most cell types)

What does a low concentration of Shh (farthest from the notochord) induce?

Interneurons (more dorsal cell types, e.g. V1)

What is the epithelial-to-mesenchymal transition sequence for neural crest cells?

Delamination, migration, reaggregation, differentiation

What does cranial neural crest give rise to?

Cartilage, bone, cranial ganglia, and connective tissue of the face

What does cardiac neural crest give rise to?

The septum of the outflow tract of the heart and the wall of large arteries

What does vagal neural crest give rise to?

Enteric ganglia of the gut

What does trunk neural crest give rise to?

Melanocytes, dorsal root ganglia, sympathetic ganglia, adrenal medulla

What does sacral neural crest give rise to?

Enteric ganglia of the distal colon

What structure does the cardiac neural crest form that separates the pulmonary artery from the aorta?

The aorticopulmonary septum (truncus arteriosus septum)

What two supporting cell types of the peripheral nervous system are derived from neural crest?

Schwann cells and satellite cells

What is Treacher Collins syndrome also called?

Mandibulofacial dysostosis

What gene is mutated in Treacher Collins syndrome, and what protein does it encode?

TCOF1, encoding the nucleolar protein Treacle1

What is the inheritance pattern and incidence of Treacher Collins syndrome?

Autosomal dominant, 1:10,000 live births

List four clinical features of Treacher Collins syndrome

Hypoplasia of facial bones (mandible/zygomatic complex), downward slanting palpebral fissures, defective middle ear ossicles (hearing loss), dental malocclusion with reduced/abnormally spaced teeth

What cellular defect underlies Treacher Collins syndrome craniofacial hypoplasia?

Neural crest cell death

What is Hirschsprung's disease?

Aganglionic megacolon due to absence of enteric neurons in the colon, a neurocristopathy

What genes are mutated in Hirschsprung's disease?

SOX10 and Endothelin Receptor B

What syndrome is Hirschsprung's disease often associated with, and what are its features?

Waardenburg-Shah syndrome — pigmentation defects (e.g. white forelock) and deafness

What are cranial placodes?

Thickenings of the cephalic embryonic ectoderm that contribute to the sensory organs

Name the two mechanisms by which cranial placodes form

Invagination and delamination

Which placodes form by invagination?

Adenohypophyseal, lens, otic, olfactory

Which placodes form by delamination?

Trigeminal and epibranchial

What does the lens placode give rise to?

The lens (vision)

What does the otic placode give rise to?

The inner ear (hearing/balance)

What does the olfactory placode give rise to?

The olfactory epithelium (smell)

What structure does the adenohypophyseal placode form via Rathke's pouch?

The adenohypophysis (anterior pituitary)

What do trigeminal placodes contribute to?

The ophthalmic and maxillomandibular lobes of the trigeminal ganglion (CN V)

What do epibranchial placodes contribute to?

Geniculate (CN VII), petrosal (CN IX), and nodose (CN X) ganglia