In multicellular organisms, cell-cell communication involving secreted factors is an essential means by which cells influence the fates of neighboring cells. Members of the transforming growth factor-_ (TGF-_) superfamily play a key role in organizing the body axis during embryogenesis in flies, frogs and mammals. We are interested in understanding the role of two TGF-_ related genes, screw (scw) and decapentaplegic (dpp), in specifying cell fate during embryonic development in the fruitfly Drosophila. Since the TGF-_ signaling pathway is evolutionarily conserved, findings from a genetically tractable organisms like Drosophila can provide insights into the mechanism of action of TGF-_ proteins in other organisms, including humans. We have cloned the scw gene and shown that although scw transcripts are ubiquitously expressed, the protein is only required in dorsal cells. It is likely that Scw may be activated in a subset of the cells where it is expressed because of its interaction with other genes involved in patterning the embryo. We are using molecular genetic tools and biochemical techniques to test how Scw activity is modulated post-translationally.
Another focus in the lab is to understand the mechanism of TGF-_ signal transduction. Despite significant progress in identifying the receptors that bind TGF-_ ligands, the mechanism by which cells transduce these signals and their cellular responses, have not been defined in any system. We have recently identified the schnurri (shn) gene as an early nuclear target in the Dpp/TGF-_ signaling pathway. Shn resembles a family of mammalian transcription factors, and is homologous to the human major histocompatibility binding proteins, MBP-1 and MBP-2. Our data indicate that shn activity rather than its transcription, is regulated by Dpp. Future experiments will center on understanding how Shn is activated in response to Dpp.