molecular reg of development-theisen Flashcards
growth and differentiation factors
FGFs- fibroblast growth factors
hedgehog proteins-desert, indian and sonic
transforming growth factor beta (TGF-beta)- superfamily
-bone morphogenetic proteins (BMP)
WNT proteins
transcription factors
HOX genes and homeodomain proteins T-box gene family Helix-loop-helix zinger finger proteins -sox genes -WT1
Hox genes
39 homologous in 4 clusters on 4 chromosomes. play prominent role in craniocaudal segmentation of the body. 3’ genes expressed earlier than 5’
Hox gene regulation
a bunch of retinoic acid (Vitamin A derivative, acutane) screws up the body
mutations in hox genes
loss of function=posterior to anterior transformations
gain of function=anterior to posterior transformations
Pax gene family
9 known members. critical role in formation of tissues and organs during embryonic development, and normal function of certain cells after birth.
Pax gene disorder
aniridia (complete or partial absence of iris)
lim proteins
involved in formation of virtually all body segments.
absence of certain proteins results in headless mammilian embryos
Dlx genes
6 members, important role in patterning of outgrowing appendages in early embryogenesis, and morphogenesis of the jaws and inner ear
Msx genes
6 types in humans. Prenatally-general inhibitors of cell differentiation.
postnatally-maintain proliferative capacity of tissues.
involved in epithelial-mesenchymal interactions in face and limbs
Msx disease
craniosynostosis (fusion of skull where it shouldnt)
t-box genes (Tbx)
100 (18) in humans. important in mesodermal germ layer development and in specifying whether limbs will be forelimb or hindlimb
Helix-loop-helix transcription factors
2 alpha-helices separated by a short amino acid loop with adjacent basic regions. Common in tf’s that regulate myogenesis (formation of muscle tissue)
Fox gene family (forkhead)
over 100 members. regulate the expression of genes involved in cell growth, proliferation, differentiation and longevity. Have pioneering transcription activity by binding condensed chromatin during cell differentiation. (winged helix is forkhead box)
FOXP2
positive selection. first gene associated with disorders of speech and lang. development.
Zink finger proteins (TF)
regulate myogenesis, implicated in bone, cartilage, or tooth development. zink deficiency is known to result in growth retardation and pathogenesis of osteoporosis.
SOX genes
greater than 20 members. SoxA=SRY, sex determining region of Y chromosome. zinc finger TF
SOX9 gene mutation
campomelic dysplasia. Short legs, dislocated hips, underdeveloped shoulder blades, 11 pairs of ribs, bone abnormalities in the neck and clubfeet. Ambiguous genitalia. Laryngeotracheal malacia (softened cartilage in respiratory system). zinc finger TF
WT1
wilm’s tumor suppressor gene. plays a role in kidney and gonadal development. Zinc finger TF
FGFs (fibroblast growth factors)
associated with ECM and must bind to heparan sulfate to activate receptors. Involved in angiogenesis, wound healing, embryonic development, and endocrine pathways
SHH- Sonic hedgehog protein
regulation of vertebrate organogenesis, facial and limb patterning and organization of the brain. Controls division of adult stem cells
IHH- indian hedgehog
chondrocyte differentiation, proliferation and maturation esp. during endochondral ossification
DHH- Desert hedgehog
defects associated with partial gonadal dysgenesis (PGD) accompanied by polyneuropathy
Hedgehog proteins
binds to patched receptor (PTCH) which is bound to transmembrane protein (smoothened. SMO)
Wnt
gastrulation and organogenesis. Also interacts with ECM components and cell-cell interactions during embryogenesis. signal is transduced by beta-catenin
Wnt signal member APC
colorectal cancer
