Fat facets deubiquitylation of Medea/Smad4 modulates interpretation of a Dpp morphogen gradient

The ability of secreted Transforming Growth Factor beta (TGF beta) 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 TGF beta signals at the level of Smad4 ubiquitylation is a conserved mechanism required for proper implementation of a morphogen gradient.