A Gain-of-Function Mutant of patched Dissects Different Responses to the Hedgehog Gradient

Abstract

The Hedgehog (Hh) signal has an inductive role during Drosophila development. Patched is part of the Hedgehog–receptor complex and shows a repressive function on the signaling cascade, which is alleviated in the presence of Hh. Herein, we identify the first dominant gain-of-function allele of patched, Confused (patchedCon). Analysis of the patchedCon allele led us to uncover novel features of the reception and function of the Hh signal. At least three different regions of gene expression were identified and a gradient of cell affinities was established in response to Hh. A new state of Cubitus interruptus activity responsible for the activation of araucan and caupolican genes of the iroquois complex, independent of Fused kinase function, was shown. In the disc, patchedCon behaved like fused mutants and was rescued by Suppressor of fused mutations. However, fused mutants are embryonic lethal while patchedCon is not, suggesting that Patched could interpret Hedgehog signaling differently in the embryo and in the adult.