First Author | Zhulyn O | Year | 2015 |
Journal | Dev Biol | Volume | 397 |
Issue | 2 | Pages | 191-202 |
PubMed ID | 25448692 | Mgi Jnum | J:218166 |
Mgi Id | MGI:5616942 | Doi | 10.1016/j.ydbio.2014.10.023 |
Citation | Zhulyn O, et al. (2015) Ptch2 shares overlapping functions with Ptch1 in Smo regulation and limb development. Dev Biol 397(2):191-202 |
abstractText | 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. |