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Fig. 8. The effects of DHCR7 impinges on Smo. (A-F) Microinjection of
DHCR7R350W mutant inhibits endogenous Shh signaling.
Embryos microinjected with 1 ng of DHCR7R350W mRNA
inhibits the expression of FoxA2, Shh and Ptc-1.
(G-I) Microinjection of mRNA (500 pg) encoding dnPKA inhibits the
cyclopic phenotype caused by DHCR7R350W. (J) Control
uninjected embryo. (K) Smo-M2 rescues DHCR7-mediated Hh signaling
inhibition. Embryos were co-injected with 8x3'Gli-BS Luc together
with Chordin, Shh-N, DHCR7 or Smo-M2 mRNA (0.5 ng), or in
combination, and the reporter gene activity was measured. (L)
DHCR7IVS8-1G>C blocks Gli reporter activation mediated by
Smo-M2. Embryos were co-injected with Gli reporter together with Chordin,
DHCR7IVS8-1G>C or Smo-M2 mRNA, or in combination,
and reporter gene activity was measured. (M) Model for the role of
DHCR7 in Shh signaling. Shh inactivates Ptc, thus permitting the activation of
Smo. Activated Smo transmits a Shh signal to activate Gli protein. PKA
inhibits Gli activation. DHCR7 inhibits Shh signaling either at the level of
or downstream of Smo.
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