Genetics, Vol 142, 493-505, Copyright © 1996

INVESTIGATIONS

Molecular Lesions Associated With Alleles of decapentaplegic Identify Residues Necessary for TGF-{beta}/BMP Cell Signaling in Drosophila melanogaster

K. Wharton, R. P. Ray, S. D. Findley, H. E. Duncan and W. M. Gelbart
Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138

We have identified the molecular lesions associated with six point mutations in the Drosophila TGF-{beta} homologue decapentaplegic (dpp). The sites of these mutations define residues within both the pro and ligand regions that are essential for dpp function in vivo. While all of these mutations affect residues that are highly conserved among TGF-{beta} superfamily members, the phenotypic consequences of the different alleles are quite distinct. Through an analysis of these mutant phenotypes, both in cuticle preparations and with molecular probes, we have assessed the functional significance of specific residues that are conserved among the different members of the superfamily. In addition, we have tested for conditional genetic interactions between the different alleles. We show that two of the alleles are temperature sensitive for the embyronic functions of dpp, such that these alleles are not only embryonic viable as homozygotes but also partially complement other dpp hypomorphs at low temperatures. Our results are discussed with regard to in vitro mutagenesis data on other TGF-{beta}-like molecules, as well as with regard to the regulation of dpp cell signaling in Drosophila.

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