Pintar - Teratogens Flashcards
Aneuploidy
Wrong number of chromosomes; lethal in fetus except trisomy 13/18, since they contain little genetic material
Trisomy 13
- midline defects
- cleft palate
- CNS malformations
- microopthalmia (small eyes)
- HOLOPROSENCEPHALY (one brain ventricle instead of 2)
Trisomy 18
- Clenched hands
- low-set ears
- “ROCKER BOTTOM FEET”
- Prominent occipital lobe
Thalidomide
Teratogen, causes PHOCOMELIA (absence of limb, but proper hand development)
TGF-B Signaling
TGF-B binds serine/threonine kinase receptor, causes their dimerization, phosphorylation, phosphorylate Smads. Smads binds target genes (TGF-B response elements), cause transcription.
-antagonists (Noggin, Chordin) bind receptor, prevent dimerization
FGF-Heparin Sulfate
Fibroblast Growth Factor, bound to heparin sulfate (GAG) on proteoglycan. heparin sulfate brings FGF to tyrosine kinase receptor, then same as TGF-B
Brachyury
Like nodal, responsible for mesoderm formation
FGF function (2)
1) Induces primitive node nodal expression, causing L/R development
2) promotes chordin/noggin expression, inhibiting BMP-4 and promoting mesoderm production
Retinoic Acid
produced in SMALL amounts in parts of embryo, elsewhere degraded. If overexpressed, causes reduced posterior development. This is since it has tug-of-war with FGF, it’s expressed anterior and FGF posterior, FGF gradually overpowered in posterior direction, allowing FGF time to develop posterior by activating Hox genes before shut off. But if RA is overexpressed, FGF shuts off too early, Hox deletion, posterior can’t develop
Nodal and AVE
Nodal is TGF-B protein key to formation of mesoderm. Nodal also produces AVE (anterior visceral endoderm, basically head). AVE will inhibit nodal around the body using BMP-4 inhibitor. Need nodal to be expressed at primitive node to form mesoderm, so chordin and noggin will inhibit BMP-4 to free nodal. Goosecoid also important for anterior development of node.
