title: Fat facets deubiquitylation of Medea/Smad4 modulates interpretation of a Dpp morphogen gradient.
abstract: The ability of secreted Transforming Growth Factor β (TGFβ) proteins to act as morphogens dictates that their influence be strictly regulated. Here, we report that maternally contributed fat facets (faf; a homolog of USP9X/FAM) is essential for proper interpretation of the zygotic Decapentaplegic (Dpp) morphogen gradient that patterns the embryonic dorsal-ventral axis. The data suggest that the loss of faf reduces the activity of Medea (a homolog of Smad4) below the minimum necessary for adequate Dpp signaling and that this is likely due to excessive ubiquitylation on a specific lysine. This study supports the hypothesis that the control of cellular responsiveness to TGFβ signals at the level of Smad4 ubiquitylation is a conserved mechanism required for proper implementation of a morphogen gradient.
authors: School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501, USA.
authors: Michael J
authors: MJ
authors: Stinchfield
authors: Norma T
authors: NT
authors: Takaesu
authors: Janine C
authors: JC
authors: Quijano
authors: Ashley M
authors: AM
authors: Castillo
authors: Nina
authors: N
authors: Tiusanen
authors: Osamu
authors: O
authors: Shimmi
authors: Elena
authors: E
authors: Enzo
authors: Sirio
authors: S
authors: Dupont
authors: Stefano
authors: S
authors: Piccolo
authors: Stuart J
authors: SJ
authors: Newfeld
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D010450:Endopeptidases / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C112504:Med protein, Drosophila; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; C064196:dpp protein, Drosophila; D010450:Endopeptidases; C059237:ubiquitin-Nalpha-protein hydrolase