| First Author | Butterfield NC | Year | 2009 |
| Journal | Development | Volume | 136 |
| Issue | 20 | Pages | 3515-24 |
| PubMed ID | 19783740 | Mgi Jnum | J:153595 |
| Mgi Id | MGI:4365848 | Doi | 10.1242/dev.037507 |
| Citation | Butterfield NC, et al. (2009) Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb. Development 136(20):3515-24 |
| abstractText | 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. |
