Fig. 8

Phenotypic reversal by Hh inhibitors.

(A) Reversal of pancreatic phenotypes in embryos. Embryos were treated with either HPI-4 or cyclopamine from 32 hpf until 5 dpf. Neither HPI-4 nor cyclopamine at the indicated concentrations impairs pancreatic development in controls. A well-formed pancreas in control produces a 1.5 to 2.0 times longer posterior pancreas compared to the head. Hh-expression induces a short and slender posterior pancreas showing the ratio between the body and head by approximately 1.0. By the criterion for reversal of the 1.5 times or longer posterior pancreas, the Hh-induced pancreatic phenotypes are effectively reversed by either HPI-4 or cyclopamine treatment. (B). Prevention of pancreatic fibrosis by a long-term treatment with Hh inhibitors. 12 day-old Ihha-expressing larvae were treated with Hh inhibitors for up to 6 weeks. In the HPI-4 treated group (12 out of 16 survived), there is no evidence of pancreatic fibrosis but a somewhat prominent fatty infiltration (red arrows). Contrary to HPI-4, cyclopamine failed to inhibit pancreatic fibrosis in the surviving 11 zebrafish out of 14. Bars, 50 μm.