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Publication : Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation.

First Author  Izzi L Year  2011
Journal  Dev Cell Volume  20
Issue  6 Pages  788-801
PubMed ID  21664577 Mgi Jnum  J:173603
Mgi Id  MGI:5049791 Doi  10.1016/j.devcel.2011.04.017
Citation  Izzi L, et al. (2011) Boc and gas1 each form distinct shh receptor complexes with ptch1 and are required for shh-mediated cell proliferation. Dev Cell 20(6):788-801
abstractText  Hedgehog (Hh) proteins regulate important developmental processes, including cell proliferation and differentiation. Although Patched acts as the main Hh receptor in Drosophila, Hh signaling absolutely requires the additional Hh-binding proteins Ihog and Boi. Here we show that, unexpectedly, cerebellar granule neuron progenitors (CGNPs) lacking Boc and Cdon, the vertebrate orthologs of Ihog and Boi, still proliferate in response to Hh. This is because in their absence, Gas1, an Hh-binding protein not present in Drosophila, mediates Hh signaling. Consistently, only CGNPs lacking all three molecules-Boc, Cdon, and Gas1-have a complete loss of Hh-dependent proliferation. In a complementary manner, we find that a mutated Hh ligand that binds Patched1 but not Boc, Cdon, or Gas1 cannot activate Hh signaling. Together, this demonstrates an absolute requirement for Boc, Cdon, and Gas1 in Hh signaling and reveals a distinct requirement for ligand-binding components that distinguishes the vertebrate and invertebrate Hh receptor systems.
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