Robustness of the Dpp morphogen activity gradient depends on negative feedback regulation by the inhibitory Smad, Dad

Yuri Ogiso, Kazuhide Tsuneizumi, Naoki Masuda, Makoto Sato, Tetsuya Tabata*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)668-678
Number of pages11
JournalDevelopment Growth and Differentiation
Issue number5
Publication statusPublished - 2011 Jun
Externally publishedYes


  • Decapentaplegic
  • Drosophila
  • Inhibitory smad
  • Morphogen
  • Robustness

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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