DAUGHTERS AGAINST DPP MODULATES DPP ORGANIZING ACTIVITY IN DROSOPHILAWING DEVELOPMENT

The family of TGF-beta signalling molecules play inductive roles in va rious developmental contexts(1). One member of this family, Drosophila Decapentaplegic (Dpp)(2) serves as a morphogen that patterns both the embryo(3,1) and adult(4,5). We have now isolated a gene, Daughters ag ainst dpp (Dad), whose transcription is induced by Dpp, Dad shares wea k homology with Drosophila Mad (Mothers against dpp)(6), a protein req uired for transduction of Dpp signals. In contrast to Mad or the activ ated Dpp receptor, whose overexpression hyperactivates the Dpp signall ing pathway, overexpression of Dad blocks Dpp activity, Expression of Dad together with either Mad or the activated receptor rescues phenoty pic defects induced by each protein alone. Dad can also antagonize the activity of a vertebrate homologue of Dpp, bone morphogenetic protein (BMP-4; ref. 7), as evidenced by induction of dorsal or neural fate f ollowing overexpression in Xenopus embryos. We conclude that the patte rn-organizing mechanism governed by Dpp involves a negative-feedback c ircuit in which Dpp induces expression of its own antagonist, Dad, Thi s feedback loop appears to be conserved in vertebrate development.