A gain-of-function mutant of patched dissects different responses to the Hedgehog gradient

The Hedgehog (Hh) signal has an inductive role during Drosophila developmen t. Patched is part of the Hedgehog-receptor complex and shows a repressive function on the signaling cascade, which is alleviated in the presence of H h. Herein, we identify the first dominant gain-of-function allele of patche d Confused (patched(Con)). Analysis of the patched(Con) allele led us to un cover novel features of the reception and function of the Hh signal. At lea st three different regions of gene expression were identified and a gradien t of cell affinities was established in response to Hh. A new state of Cubi tus interruptus activity responsible for the activation of araucan and caup olican genes of the iroquois complex, independent of Fused kinase function, was shown. In the disc, patched(Con) behaved like fused mutants and was re scued by Suppressor of fused mutations. However, fused mutants are embryoni c lethal while patched(Con) is not, suggesting that Patched could interpret Hedgehog signaling differently in the embryo and in the adult. (C) 2000 Ac ademic Press.