MOTHERS AGAINST DPP ENCODES A CONSERVED CYTOPLASMIC PROTEIN REQUIRED IN DPP TGF-BETA RESPONSIVE CELLS/

The proteins necessary for signal transduction in cells responding to ligands of the TGF-P family are largely unknown. We have previously id entified Mad (Mothers against dpp), a gene that interacts with the TGF -P family member encoded by decapentaplegic (dpp) in Drosophila. Assay of Mad's role in the DPP-dependent events of embryonic midgut develop ment demonstrates that Mad is required for any response of the viscera l mesoderm or endoderm to DPP signals from the visceral mesoderm. Repl acement of the normal DPP promoter,vith a heterologous (hsp70) promote r fails to restore DPP-dependent responses in Mad mutant midguts. Expe riments utilizing Mad transgenes regulated by tissue-specific promoter s show that MAD is required specifically in cells responding to DPP. I mmunohistochemical studies localize MAD to the cytoplasm in all tissue s examined. Experiments in Xenopus embryos demonstrate that Drosophila MAD can function in the signaling pathway of BMP-4, a vertebrate homo log of dpp. Based on these results, we propose that Mad is a highly co nserved and essential element of the DPP signal transduction pathway.