SMOOTHENED ENCODES A SERPENTINE PROTEIN REQUIRED FOR HEDGEHOG SIGNALING

MEMBERS of the Hedgehog family of secreted proteins control a number o f important inductive interactions in the development of both vertebra tes and Drosophila(1), but little is known about the ways in which the ir signalling activities are transduced. In Drosophila, hedgehog is on e of the segment-polarity genes, mutations of which disrupt the patter n and polarity of individual embryonic segments(2) and their adult der ivatives(3); several of these genes have been implicated in transducti on of the hedgehog signal(4-6). Here we show that the segment-polarity gene smoothened is required for the response of cells to hedgehog sig nalling during the development of both the embryonic segments and imag inal discs. Sequence analysis of the smoothened transcription unit rev eals a single open reading frame encoding a protein with seven putativ e transmembrane domains. This structure is typical of G-protein-couple d receptors, suggesting that the Smoothened protein may act as a recep tor for the Hedgehog ligand.