title: Transgenic analysis of the Smad family of TGF-beta signal transducers in Drosophila melanogaster suggests new roles and new interactions between family members.
abstract: Smad signal transducers are required for transforming growth factor-beta-mediated developmental events in many organisms including humans. However, the roles of individual human Smad genes (hSmads) in development are largely unknown. Our hypothesis is that an hSmad performs developmental roles analogous to those of the most similar Drosophila Smad gene (dSmad). We expressed six hSmad and four dSmad transgenes in Drosophila melanogaster using the Gal4/UAS system and compared their phenotypes. Phylogenetically related human and Drosophila Smads induced similar phenotypes supporting the hypothesis. In contrast, two nearly identical hSmads generated distinct phenotypes. When expressed in wing imaginal disks, hSmad2 induced oversize wings while hSmad3 induced cell death. This observation suggests that a very small number of amino acid differences, between Smads in the same species, confer distinct developmental roles. Our observations also suggest new roles for the dSmads, Med and Dad, in dActivin signaling and potential interactions between these family members. Overall, the study demonstrates that transgenic methods in Drosophila can provide new information about non-Drosophila members of developmentally important multigene families.
authors: Department of Biology, Arizona State University, Tempe, Arizona 85287, USA.
authors: R M
authors: RM
authors: Marquez
authors: M A
authors: MA
authors: Singer
authors: N T
authors: NT
authors: Takaesu
authors: W R
authors: WR
authors: Waldrip
authors: Y
authors: Y
authors: Kraytsberg
authors: S J
authors: SJ
authors: Newfeld
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C108633:Dad protein, Drosophila; D029721:Drosophila Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D019476:Insect Proteins; C112506:MAD protein, Drosophila; C112504:Med protein, Drosophila; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D029701:Saccharomyces cerevisiae Proteins; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta