title: Robustness of the Dpp morphogen activity gradient depends on negative feedback regulation by the inhibitory Smad, Dad.
abstract: Developmental patterning relies on morphogen concentration gradients, which generally provide invariable positional information despite genetic fluctuations. Theoretical studies have predicted robust patterning; however, little experimental evidence exists to support this idea. In this report, we examine the robustness of the Decapentaplegic (Dpp) (a Drosophila homologue of bone morphogenetic protein [BMP]) activity gradient in the presence of fluctuations in Dpp receptor levels. Dpp activity can be measured by the degree of phosphorylation of Mothers against dpp (Mad), a major signal transducer. We determined that phosphorylated Mad (pMad) levels remain constant when an extra copy of thickveins (tkv), which encodes the receptor, is introduced into the wild-type background. Higher Tkv levels, expressed under the control of an artificial promoter, result in constant pMad levels. This prompted us to study the mechanisms that underlie pMad level maintenance even when Tkv levels are increased. We focused on the inhibitory Smad, daughters against dpp (dad), which is induced by Dpp signaling and negatively regulates Dpp activity. In the absence of dad, pMad levels significantly increase when Tkv levels increase. These results suggest that Dpp activity gradient robustness when Tkv levels increase depends, at least in part, on negative feedback regulation by dad.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ogiso
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Tsuneizumi
authors.forename: Naoki
authors.initials: N
authors.lastname: Masuda
authors.forename: Makoto
authors.initials: M
authors.lastname: Sato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tabata
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D005453:Fluorescence; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018613:Microscopy, Confocal; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: C108633:Dad protein, Drosophila; D029721:Drosophila Proteins; D011956:Receptors, Cell Surface; C064196:dpp protein, Drosophila; C090169:tkv protein, Drosophila; D017346:Protein Serine-Threonine Kinases