Transgenic analysis of the Smad family of TGF-beta signal transducers in Drosophila melanogaster suggests new roles and new interactions between family members

Smad signal transducers are required for transforming growth factor-beta -m ediated developmental events in man) organisms including humans. However, t he roles of individual human Smad genes (hSmads) in development al-e largel y unknown. Our hypothesis is that an hSmad performs developmental roles ana logous to those of the most similar Drosophila Smad gene (dSmad). Mie expre ssed six hSmad and four dSmad transgenes in Drosophila melanogaster using t he Gal4/UAS system and compared their phenotypes. Phylogenetically related human and Drosophila Smads induced similar phenotypes supporting the hypoth esis. In contrast. two nearly; identical hSmads generated distinct phenotyp es. When expressed in wing imaginal disks, hSmad2 induced oversize wings wh ile hSmad3 induced cell death. This observation suggests that a vel) small number of amino acid differences, between Smads in the same species, confer distinct developmental roles. Our observations also suggest new roles for the dSmads. Med and Dad, in dActivin signaling and potential interactions b etween these family members. Overall. the study demonstrates that transgeni c methods in Drosophila carl provide new information about non-Drosophila m embers of developmentally important multigene families.