TGF-beta family signal transduction in Drosophila development: From Mad toSmads

The transforming growth factor-beta (TGF-beta) superfamily encompasses a la rge group of soluble extracellular proteins that are potent regulators of d evelopment in both vertebrates and invertebrates. Drosophila TGF-beta famil y members include three proteins with homology to vertebrate bone morphogen etic proteins (BMPs): Decapentaplegic (Dpp), Screw, and Glass bottom boat-6 0A. Genetic studies of Dpp signaling led to the identification of Smad prot eins as central mediators of signal transduction by TGF-beta family members . Work in mammalian tissue culture has elucidated a biochemical model for s ignal transduction, in which activation of receptor serine-threonine kinase activity leads to phosphorylation of specific Smad proteins and translocat ion of heteromeric Smad protein complexes to the nucleus. Once in the nucle us Smad proteins interact with other DNA binding proteins to regulate trans cription of specific target genes. Dissection of Dpp-response elements from genes expressed during embryonic mesoderm patterning and midgut morphogene sis provides important insights into the contributions of Smad proteins and tissue-specific transcription factors to spatial regulation of gene expres sion. Genetic studies in Drosophila are now expanding to include multiple B MP ligands and receptors and have uncovered activities not explained by the current signal transduction model. Identification of more ligand sequences and demonstration of a functional Drosophila activin-like signal transduct ion pathway suggest that all TGF-beta signal transduction pathways are pres ent in flies. (C) 1999 Academic Press.