THE DROSOPHILA GENE MEDEA DEMONSTRATES THE REQUIREMENT FOR DIFFERENT CLASSES OF SMADS IN DPP SIGNALING

Signals from transforming growth factor-beta (TGF-beta) ligands are tr ansmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previou s identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila clas s II Smad, Medea, a close homolog of the human tumor-suppressor gene D PC4, Embryos from germline clones of both Medea and Mad (a class I Sma d) are ventralized, as are embryos null for the TGF-P-like ligand deca pentaplegic (dpp). Loss of Medea also blocks dpp signaling during late r development, suggesting that Medea, like Mad, is universally require d for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different s ignaling properties - upon activation of the Dpp pathway, Mad is requi red to actively translocate Medea into the nucleus. These results prov ide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.