GENETIC-CHARACTERIZATION AND CLONING OF MOTHERS AGAINST DPP, A GENE REQUIRED FOR DECAPENTAPLEGIC FUNCTION IN DROSOPHILA-MELANOGASTER

The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a gr owth factor that belongs to the transforming growth factor-beta (TGF-b eta) superfamily and that plays a central role in multiple cell-cell s ignaling events throughout development. Through genetic screens we are seeking to identify other functions that act upstream, dowstream or i n concert with dpp to mediate its signaling role. We report here the g enetic characterization and cloning of Mothers against dpp (Mad), a ge ne identified in two such screens. Mad loss-of-function mutations inte ract with dpp alleles to enhance embryonic dorsal-ventral patterning d efects, as well as adult appendage defects, suggesting a role for Mad in mediating some aspect of dpp function. In support of this, homozygo us Mad mutant animals exhibit defects in midgut morphogenesis, imagina l disk development and embryonic dorsal-ventral patterning that are ve ry reminiscent of dpp mutant phenotypes. We cloned the Mad region and identified the Mad transcription unit through germline transformation rescue. We sequenced a Mad cDNA and identified three Mad point mutatio ns that alter the coding information. The predicted MAD polypeptide la cks known protein motifs, but has strong sequence similarity to three polypeptides predicted from genomic sequence from the nematode Caenorh abditis elegans. Hence, MAD is a member of a novel, highly conserved p rotein family.