| First Author | Holtz AM | Year | 2013 |
| Journal | Development | Volume | 140 |
| Issue | 16 | Pages | 3423-34 |
| PubMed ID | 23900540 | Mgi Jnum | J:199287 |
| Mgi Id | MGI:5502237 | Doi | 10.1242/dev.095083 |
| Citation | Holtz AM, et al. (2013) Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning. Development 140(16):3423-34 |
| abstractText | Hedgehog (HH) signaling is essential for vertebrate and invertebrate embryogenesis. In Drosophila, feedback upregulation of the HH receptor Patched (PTC; PTCH in vertebrates), is required to restrict HH signaling during development. By contrast, PTCH1 upregulation is dispensable for early HH-dependent patterning in mice. Unique to vertebrates are two additional HH-binding antagonists that are induced by HH signaling, HHIP1 and the PTCH1 homologue PTCH2. Although HHIP1 functions semi-redundantly with PTCH1 to restrict HH signaling in the developing nervous system, a role for PTCH2 remains unresolved. Data presented here define a novel role for PTCH2 as a ciliary localized HH pathway antagonist. While PTCH2 is dispensable for normal ventral neural patterning, combined removal of PTCH2- and PTCH1-feedback antagonism produces a significant expansion of HH-dependent ventral neural progenitors. Strikingly, complete loss of PTCH2-, HHIP1- and PTCH1-feedback inhibition results in ectopic specification of ventral cell fates throughout the neural tube, reflecting constitutive HH pathway activation. Overall, these data reveal an essential role for ligand-dependent feedback inhibition of vertebrate HH signaling governed collectively by PTCH1, PTCH2 and HHIP1. |
