Download Hh-Notch-4061 2016

Hedgehog and Notch signaling
Hedgehogs: role in vertebrate development and
some Human congenital malformation syndromes
Drosophila Hedgehog (Hh) pointy denticles
Tabin’s lab identfied 3 Vertebrate genes with homology to Hh:
Sonic Hedgehog (Shh) Widespread useage in dev. Particularly in NT and
limb development
Desert Hedgehog (Dhh) Sertoli cells mice -/- defective spermatogenesis
Indian Hedgehog (Ihh) gut and cartilage
Figure 3.25 Hedgehog signal transduction pathway
Figure 3.26 Sonic hedgehog is shown by in situ hybridization to be expressed in the nervous system (red
arrow), gut (blue arrow), and limb bud (black arrow) of a 3-day chick embryo
Model of major postulated interactions in the
patterning of the somite
Signaling between NT, Nc and somite
Inherited congenital malformation syndromes
in Humans
Grieg cephalopolysyndactyly: high forehead and
increased # of digits(results from a non functional truncation
of the Gli3 protein)
Pallister Hall syndrome lethal shortly after birth- Gli3 DBD intact
but no TAD (Dom Neg)
Ectopic activation of Hh pathway in somatic tissues:
Eg heritable mut in Patched gene (no inhibition of Smo):
Developmental abnormalities, fused fingers, rib and facial defects
Basal cell carcinomas
Skeletal pattern of the chick wing
Sonic hedgehog protein is expressed in the ZPA
Head of a cyclopic lamb born of a ewe who had eaten Veratrum californicum early in
pregnancy
Figure 3.33 Mechanism of Notch activity (Part 1)
Figure 3.33 Mechanism of Notch activity (Part 2)