Pintar - Neural Crest

Question 1

Initiation of Neural Crest Migration

Answer 1

NC cells transform from epithelia–>mesenchyme by losing cadherins - no longer have cell/cell adhesion, they’re free to move into hyaluronic acid of cavities

Question 2

Ligand-Receptor systems of neural crest migration

Answer 2

Border specifier genes produce chemoattractant ligands which the NC cell’s receptors bind; by sequentially activating the ligands in posterior compartments, NC cells migrate. Ex:

• c-kit receptor and Steel factor ligand in pigment NC migration
• c-ret receptor and GDNF in enteric nervous system-forming NCs

Question 3

Neural Crest Formation

Answer 3

BMP-4 supression near midline (by noggin, chordin, FGF) allows ectoderm to pinch off and form neural tube. Neural crest is cells above neural tube. Those cells can then differentiate and migrate to tissues.
More detail: Low BMP induces “snail”, which activates border specifier genes (transcription factors for NC chemoattractors like c-kit), which cause transcription factor cascade attracting NC cells to tissues in sequential order toward posterior.

Question 4

Hirschsprung’s Disease

Answer 4

MEGACOLON resulting from deficiency of enteric ganglia formation (lack of neural crest cell migration), due to deficiency of c-Ret receptor in NC cells or GDNF

Question 5

DiGeorge’s Syndrome (DGS) symptoms

Answer 5

• defects in cardiac outflow and tracts
• thymus and hypothyroid dysplasia causing immune deficiency
• laryngeo-trachial anomalies
• craniofacial anomalies
• cleft palate
• micrognathia (small jaw)
• low-set ears

Question 6

DGS mechanism

Answer 6

Defect in Pharyngeal Arch development due to chromosome 22 mutation in Tbx-1 gene, affects NC migration to area

Question 7

Tbx-1 pathway

Answer 7

Shh activates Tbx-1, which activates FGF

Question 8

Other genes causing DGS

Answer 8

crkl. Near Txb1 on chromosome, affects NC cell (TGF-B and FGF signaling). Different from tbx1 since affects NC-cells, pharyngeal arch normal.

Question 9

Fetal Alcohol Syndrome symptoms

Answer 9

• small head size
• mental retardation
• palpebral fissures
• low nose bridge
• smooth philtrum
• congenital heart defects

Question 10

Fetal Alcohol Syndrome mechanisms

Answer 10

causes cell death in neural ridge (precursor of NC cells), plus inappropriate migration, absence and death of NC cells (and less NC cells available causes facial deformations)