{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:38:35Z","timestamp":1790235515562,"version":"4.1.0"},"reference-count":58,"publisher":"The Company of Biologists","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:p>The vertebrate hedgehog receptor patched 1 (Ptc1) is crucial for negative regulation of the sonic hedgehog (Shh) pathway during anterior-posterior patterning of the limb. We have conditionally inactivated Ptc1 in the mesenchyme of the mouse limb using Prx1-Cre. This results in constitutive activation of hedgehog (Hh) signalling during the early stages of limb budding. Our data suggest that variations in the timing and efficiency of Cre-mediated excision result in differential forelimb and hindlimb phenotypes. Hindlimbs display polydactyly (gain of digits) and a molecular profile similar to the Gli3 mutant extra-toes. Strikingly, forelimbs are predominantly oligodactylous (displaying a loss of digits), with a symmetrical, mirror-image molecular profile that is consistent with re-specification of the anterior forelimb to a posterior identity. Our data suggest that this is related to very early inactivation of Ptc1 in the forelimb perturbing the gene regulatory networks responsible for both the pre-patterning and the subsequent patterning stages of limb development. These results establish the importance of the downstream consequences of Hh pathway repression, and identify Ptc1 as a key player in limb patterning even prior to the onset of Shh expression.<\/jats:p>","DOI":"10.1242\/dev.037507","type":"journal-article","created":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T19:38:18Z","timestamp":1253907498000},"page":"3515-3524","source":"Crossref","is-referenced-by-count":51,"title":["Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb"],"prefix":"10.1242","volume":"136","author":[{"given":"Natalie C.","family":"Butterfield","sequence":"first","affiliation":[{"name":"The University of Queensland, Institute for Molecular Bioscience, Queensland 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Metzis","sequence":"additional","affiliation":[{"name":"The University of Queensland, Institute for Molecular Bioscience, Queensland 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwina","family":"McGlinn","sequence":"additional","affiliation":[{"name":"Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Bruce","sequence":"additional","affiliation":[{"name":"The University of Queensland, Institute for Molecular Bioscience, Queensland 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon J.","family":"Wainwright","sequence":"additional","affiliation":[{"name":"The University of Queensland, Institute for Molecular Bioscience, Queensland 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Wicking","sequence":"additional","affiliation":[{"name":"The University of Queensland, Institute for Molecular Bioscience, Queensland 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042621383104000_REF1","doi-asserted-by":"crossref","unstructured":"Bastida, M. 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