The transcription factor Foxc1 is necessary for Ihh–Gli2-regulated endochondral ossification
Citations Over TimeTop 10% of 2015 papers
Abstract
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.
Related Papers
- → Hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation(2009)33 cited
- → Role of Indian Hedgehog Signaling in Palatal Osteogenesis(2011)31 cited
- Molecular mechanism of Indian Hedgehog signalling in human sebocytes(2010)
- Wdpcp affects skeletogenesis via the hedgehog pathway(2015)