Dev110056 3331..3339
نویسندگان
چکیده
TheHedgehog (Hh) signaling response is regulated by the interaction of three key components that include the sonic hedgehog (Shh) ligand, its receptor patched 1 (Ptch1) and the pathway activator smoothened (Smo). Under the prevailing model of Shh pathway activation, the binding of Shh to Ptch1 (the keyShh receptor) results in the release of Ptch1-mediated inhibition of Smo, leading to Smo activation and subsequent cell-autonomous activation of the Shh response. Consistent with this model, Ptch1−/− cells show a strong upregulation of the Shh response. Our finding that this response can be inhibited by the Shh-blocking antibody 5E1 indicates that the Shh response in Ptch1 cells remains ligand dependent. Furthermore, we find that Shh induces a strong response in Ptch1;Shh cells, and thatPtch1 fibroblasts retain their ability tomigrate towards Shh, demonstrating thatPtch1 cells remain sensitive to Shh. Expression of a dominant-negative Ptch1 mutant in the developing chick neural tube had no effect on Shh-mediated patterning, but expression of a dominant-negative form of patched 2 (Ptch2) caused an activation of the Shh response. This indicates that, at early developmental stages, Ptch2 functions to suppress Shh signaling. We found that Ptch1; Ptch2 cells cannot further activate the Shh response, demonstrating that Ptch2 mediates the response to Shh in the
منابع مشابه
Representing and Reasoning with Qualitative Preferences for Compositional Systems
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