Ihog and Boi elicit Hh signaling via Ptc but do not aid Ptc in sequestering the Hh ligand.
Hedgehog (Hh) proteins are secreted molecules essential for tissue development in vertebrates and invertebrates. Hh reception via the 12-pass transmembrane protein Patched (Ptc) elicits intracellular signaling through Smoothened (Smo). Hh binding to Ptc is also proposed to sequester the ligand, limiting its spatial range of activity. In Drosophila, Interference hedgehog (Ihog) and Brother of ihog (Boi) are two conserved and redundant transmembrane proteins that are essential for Hh pathway activation. How Ihog and Boi activate signaling in response to Hh remains unknown; each can bind both Hh and Ptc and so it has been proposed that they are essential for both Hh reception and sequestration. Using genetic epistasis we established here that Ihog and Boi, and their orthologs in mice, act upstream or at the level of Ptc to allow Hh signal transduction. In the Drosophila developing wing model we found that it is through Hh pathway activation that Ihog and Boi maintain the boundary between the anterior and posterior compartments. We dissociated the contributions of Ptc from those of Ihog/Boi and, surprisingly, found that cells expressing Ptc can retain and sequester the Hh ligand without Ihog and Boi, but that Ihog and Boi cannot do so without Ptc. Together, these results reinforce the central role for Ptc in Hh binding in vivo and demonstrate that, although Ihog and Boi are dispensable for Hh sequestration, they are essential for pathway activation because they allow Hh to inhibit Ptc and thereby relieve its repression of Smo.
['Camp|Darius|D|', 'Haitian He|Billy|B|', 'Li|Sally|S|', 'Althaus|Irene W|IW|', 'Holtz|Alexander M|AM|', 'Allen|Benjamin L|BL|', 'Charron|Frédéric|F|', 'van Meyel|Donald J|DJ|']
D000818:Animals D002352:Carrier Proteins D029721:Drosophila Proteins D004331:Drosophila melanogaster D004843:Epistasis, Genetic D008024:Ligands D008562:Membrane Glycoproteins D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D008856:Microscopy, Fluorescence D000072079:Patched Receptors D000072081:Patched-1 Receptor D011485:Protein Binding D011956:Receptors, Cell Surface D011995:Recombination, Genetic D015398:Signal Transduction D013116:Spinal Cord D014921:Wings, Animal
Signaling Drosophila Morphogenesis Pattern formation