title: Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient.
abstract: By using the sensitivity of single-molecule fluorescent in situ hybridization, we have precisely quantified the levels and defined the temporal and spatial distribution of Hedgehog signaling activity during embryonic skin development and discovered that there is a Hedgehog signaling gradient along the proximal-distal axis of developing hair follicles. To explore the contribution of Hedgehog receptors Ptch1 and Ptch2 in establishing the epidermal signaling gradient, we quantitated the level of pathway activity generated in Ptch1- and Ptch1;Ptch2-deficient skin and defined the contribution of each receptor to regulation of the levels of Hedgehog signaling identified in wild-type skin. Moreover, we show that both the cellular phenotype and level of pathway activity featured in Ptch1;Ptch2-deficient cells faithfully recapitulates the Peak level of endogenous Hedgehog signaling detected at the base of developing follicles, where the concentration of endogenous Shh is predicted to be highest. Taken together, these data show that both Ptch1 and Ptch2 play a crucial role in sensing the concentration of Hedgehog ligand and regulating the appropriate dose-dependent response.
authors: Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
authors: Christelle
authors: C
authors: Adolphe
authors: Hubrecht Institute, KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors: Jan Philipp
authors: JP
authors: Junker
authors: Hubrecht Institute, KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands.
authors: Anna
authors: A
authors: Lyubimova
authors: Hubrecht Institute, KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands.
authors: Alexander
authors: A
authors: van Oudenaarden
authors: Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. Electronic address: b.wainwright@imb.uq.edu.au.
authors: Brandon
authors: B
authors: Wainwright
mesh_terms: D000818:Animals; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D000072079:Patched Receptors / Q000235:genetics / Q000378:metabolism*; D000072082:Patched-2 Receptor / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D000072079:Patched Receptors; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface