Gain-of-function Shh mutants activate Smo cell-autonomously independent of Ptch1/2 function.

08:00 EDT 22nd August 2018 | BioPortfolio

Summary of "Gain-of-function Shh mutants activate Smo cell-autonomously independent of Ptch1/2 function."

Sonic Hedgehog (Shh) signaling is characterized by non-cell autonomy; cells expressing Shh do not respond to the ligand. Here, we identify several Shh mutations that can activate the Hedgehog (Hh) pathway cell-autonomously. Cell-autonomous pathway activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of the Shh receptors Patched1 and -2. Many of the Shh mutants that gain activity fail to undergo auto processing resulting in the perdurance of the Shh pro-peptide, a form of Shh that is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smoothened, independently of Patched1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the Shh response.


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This article was published in the following journal.

Name: Mechanisms of development
ISSN: 1872-6356


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