Contribution of Ihog and Boi to the Hedgehog receptor in Drosophila. Darius Camp^1,2, Haitian He¹, Don van Meyel¹, Frédéric Charron². 1) Centre for Research in Neuroscience, McGill University, Montreal, Quebec, Canada; 2) Institut de recherches cliniques de Montréal, Montreal, Quebec, Canada.

   Hedgehog (Hh) proteins are secreted molecules that elicit intracellular signaling vital for tissue development in both vertebrates and invertebrates. Misregulation of the Hh signaling pathway is responsible for many human congenital defects and cancers. Reception of Hh at the cell surface has long been thought to be mediated by Ptc, a 12-pass transmembrane protein, which ordinarily inhibits the pathway when Hh is absent. Binding of Hh to Ptc is thought to inhibit Ptc and thereby initiate transduction of the pathway. The interaction between Hh and Ptc is also believed to be essential to sequester Hh and thus limit its spatial range of influence. In Drosophila, we and others have found that additional factors at the cell surface play an important role in the reception of Hh: Ihog and Boi are two functionally redundant type 1 transmembrane proteins of the immunoglobulin superfamily that are required for pathway activation and capable of binding both Hh and Ptc. This raises the possibility that Ihog/Boi and Ptc form a complex required for the reception of the Hh signal. However, the mechanism underlying the requirement for Ihog and Boi in the inhibition of Ptc is not known. Our work aims to better understand the Hh receptor complex by using genetic approaches to clarify the involvement Ihog/Boi and Ptc. In one model, Ihog and Boi are proposed to be important for trafficking Ptc to the plasma membrane and for high affinity Hh binding. This model predicts that cells mutant for both Ihog and Boi will be unable to bind and sequester Hh, and will fail to inhibit Ptc. We tested this model in the developing wing disc, where Hh plays an important role in anterior-posterior patterning. Our results show that Ihog and Boi, unlike Ptc, are dispensable for the sequestration of Hh. Our findings are consistent with a central role for Ptc in binding Hh in vivo. Further experiments to probe the role of Ihog and Boi in receiving and transducing the Hh signal are ongoing.