Grant: Operating Grant

The Sonic hedgehog (Shh) protein is important for diverse biological processes during embryonic development. For example, Shh functions to pattern the limbs and the nervous system. Despite its importance, the molecular mechanism underlying Shh signaling during embryonic development remains poorly understood. This proposal focuses on how the Shh signal is received by a cell. The classic view is that Shh initiates signaling by binding the protein Patched1 (Ptch1). While Ptch1 has been thought to act as the main Shh receptor for the past decades, we have recently shown that Shh signaling absolutely requires additional Shh-binding proteins. However, we do not know how these additional Shh-binding proteins function as Shh receptors. It is the goal of this project to characterize this function in detail. We anticipate that this work will bring insights into the molecular mechanism underlying diseases associated with the Shh signaling pathway and might eventually help developing therapies.