| First Author | Yoshida M | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6653 | PubMed ID | 25808752 |
| Mgi Jnum | J:221866 | Mgi Id | MGI:5641778 |
| Doi | 10.1038/ncomms7653 | Citation | Yoshida M, et al. (2015) The transcription factor Foxc1 is necessary for Ihh-Gli2-regulated endochondral ossification. Nat Commun 6:6653 |
| abstractText | Indian hedgehog (Ihh) regulates endochondral ossification in both a parathyroid hormone-related protein (PTHrP)-dependent and -independent manner by activating transcriptional mediator Gli2. However, the molecular mechanisms underlying these processes remain elusive. Here by using in vivo microarray analysis, we identify forkhead box C1 (Foxc1) as a transcriptional partner of Gli2. Foxc1 stimulates expression of Ihh target genes, including PTHrP and Col10a1, through its physical and functional interaction with Gli2. Conversely, a dominant negative Foxc1 inhibits the Ihh target gene expression. In a spontaneous loss of Foxc1 function mouse (Foxc1(ch/ch)), endochondral ossification is delayed and the expression of Ihh target genes inhibited. Moreover, the pathological Foxc1 missense mutation observed in the Axenfeld-Rieger syndrome impairs Gli2-Foxc1 association as well as Ihh function. Our findings suggest that Foxc1 is an important transcriptional partner of Ihh-Gli2 signalling during endochondral ossification, and that disruption of the Foxc1-Gli2 interaction causes skeletal abnormalities observed in the Axenfeld-Rieger syndrome. |
