title: Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster.
abstract: The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a growth factor that belongs to the transforming growth factor-beta (TGF-beta) superfamily and that plays a central role in multiple cell-cell signaling events throughout development. Through genetic screens we are seeking to identify other functions that act upstream, downstream or in concert with dpp to mediate its signaling role. We report here the genetic characterization and cloning of Mothers against dpp (Mad), a gene identified in two such screens. Mad loss-of-function mutations interact with dpp alleles to enhance embryonic dorsal-ventral patterning defects, as well as adult appendage defects, suggesting a role for Mad in mediating some aspect of dpp function. In support of this, homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very 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 mutations that alter the coding information. The predicted MAD polypeptide lacks known protein motifs, but has strong sequence similarity to three polypeptides predicted from genomic sequence from the nematode Caenorhabditis elegans. Hence, MAD is a member of a novel, highly conserved protein family.
authors.affiliation: Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Sekelsky
authors.forename: S J
authors.initials: SJ
authors.lastname: Newfeld
authors.forename: L A
authors.initials: LA
authors.lastname: Raftery
authors.forename: E H
authors.initials: EH
authors.lastname: Chartoff
authors.forename: W M
authors.initials: WM
authors.lastname: Gelbart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression; D017344:Genes, Insect; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; C112506:MAD protein, Drosophila; D012097:Repressor Proteins; D014157:Transcription Factors; C064196:dpp protein, Drosophila