Genetics, Vol 139, 1347-1358, Copyright © 1995

INVESTIGATIONS

Genetic Characterization and Cloning of Mothers against dpp, a Gene Required for decapentaplegic Function in Drosophila melanogaster

J. J. Sekelsky, S. J. Newfeld, L. A. Raftery, E. H. Chartoff and W. M. Gelbart
Present address: Section of Molecular and Cellular Biology, University of California, Davis, CA 95616.

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.

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				A. Candia, T Watabe, S. Hawley, D Onichtchouk, Y Zhang, R Derynck, C Niehrs, and K. Cho Cellular interpretation of multiple TGF-beta signals: intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads Development, January 11, 1997; 124(22): 4467 - 4480. [Abstract] [PDF]

				S. Newfeld, A Mehra, M. Singer, J. Wrana, L Attisano, and W. Gelbart Mothers against dpp participates in a DDP/TGF-beta responsive serine-threonine kinase signal transduction cascade Development, January 8, 1997; 124(16): 3167 - 3176. [Abstract] [PDF]

				R Dosch, V Gawantka, H Delius, C Blumenstock, and C Niehrs Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus Development, January 6, 1997; 124(12): 2325 - 2334. [Abstract] [PDF]

				W Shen and G Mardon Ectopic eye development in Drosophila induced by directed dachshund expression Development, January 1, 1997; 124(1): 45 - 52. [Abstract] [PDF]

				M. Singer, A Penton, V Twombly, F. Hoffmann, and W. Gelbart Signaling through both type I DPP receptors is required for anterior-posterior patterning of the entire Drosophila wing Development, January 1, 1997; 124(1): 79 - 89. [Abstract] [PDF]

				D. Andrew, A Baig, P Bhanot, S. Smolik, and K. Henderson The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the larval cuticle Development, January 1, 1997; 124(1): 181 - 193. [Abstract] [PDF]

				F Chanut and U Heberlein Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina Development, January 1, 1997; 124(2): 559 - 567. [Abstract] [PDF]

				Y. Chen, J.-J. Lebrun, and W. Vale Regulation of transforming growth factor beta - and activin-induced transcription by mammalian Mad proteins PNAS, November 12, 1996; 93(23): 12992 - 12997. [Abstract] [Full Text] [PDF]

				T. Okadome, E. Oeda, M. Saitoh, H. Ichijo, H. L. Moses, K. Miyazono, and M. Kawabata Characterization of the Interaction of FKBP12 with the Transforming Growth Factor-beta Type I Receptor in Vivo J. Biol. Chem., September 6, 1996; 271(36): 21687 - 21690. [Abstract] [Full Text] [PDF]