title: Ptch2 shares overlapping functions with Ptch1 in Smo regulation and limb development.
abstract: Ptch1 and Ptch2 are highly conserved vertebrate homologs of Drosophila ptc, the receptor of the Hedgehog (Hh) signaling pathway. The vertebrate Ptch1 gene encodes a potent tumor suppressor and is well established for its role in embryonic development. In contrast, Ptch2 is poorly characterized and dispensable for embryogenesis. In flies and mice, ptc/Ptch1 controls Hh signaling through the regulation of Smoothened (Smo). In addition, Hh pathway activation also up-regulates ptc/Ptch1 expression to restrict the diffusion of the ligand. Recent studies have implicated Ptch2 in this ligand dependent antagonism, however whether Ptch2 encodes a functional Shh receptor remains unclear. In this report, we demonstrate that Ptch2 is a functional Shh receptor, which regulates Smo localization and activity in vitro. We also show that Ptch1 and Ptch2 are co-expressed in the developing mouse limb bud and loss of Ptch2 exacerbates the outgrowth defect in the limb-specific Ptch1 knockout mutants, demonstrating that Ptch1 and Ptch2 co-operate in regulating cellular responses to Shh in vivo.
authors.affiliation: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Olena
authors.initials: O
authors.lastname: Zhulyn
authors.affiliation: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Erica
authors.initials: E
authors.lastname: Nieuwenhuis
authors.affiliation: Department of Biochemistry and Pharmaceutical Sciences, University of Toronto, Ontario, Canada M5S 1A8.
authors.forename: Yulu Cherry
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Pharmaceutical Sciences, University of Toronto, Ontario, Canada M5S 1A8.
authors.forename: Stephane
authors.initials: S
authors.lastname: Angers
authors.affiliation: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8. Electronic address: cchui@sickkids.ca.
authors.forename: Chi-chung
authors.initials: CC
authors.lastname: Hui
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005121:Extremities / Q000196:embryology*; D053823:Hedgehog Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000072086:Smoothened Receptor
chemical_list: D053823:Hedgehog Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; C000606240:Ptch1 protein, mouse; C000606241:Ptch2 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor
keywords: Apical ectodermal ridge; Mesenchyme; Patched; Patterning; Smoothened; Sonic hedgehog