Foxc1

The Transcription Factor FoxC1 Regulates Chondrogenesis Together with Gli2 through Induction of PTHrP

"the mutation of FOXC1 is shown to cause Axenfeld-Rieger syndrome (ARS) in human that is characterized by the anterior segment dysgenesis and diverse skeletal abnormalities. Whole mount in situ hybridization demonstrated evident co-expression of FoxC1 mRNA and Col2a1 in the developing limbs. Overexpression of FoxC1 induced alcian blue-positive chondrogenesis in limb bud cells in microculture. FoxC1 plays a role in chondrogenesis.
To further verify the functional role of FoxC1 in chondrogenesis, we searched for transcriptional target of FoxC1. FoxC1 had no effects on Col2a1 and Sox9 mRNA expression. On the other hand, FoxC1 increased PTHrP mRNA expression in conjunction with promoted chondrogenesis. Moreover, FoxC1 together with Gli2 further up-regulated PTHrP expression. FoxC1 [interacts with] Gli2. FoxC1 [binds directly] to the FoxC1 binding element (CTAAATAAC) in the PTHrP gene promoter. Finally, pathogenic missense mutation (Ile126Met) of FOXC1, which is responsible for ARS, suppressed PTHrP expression induced by IHH. FoxC1 promotes chondrogenesis through directly up-regulating PTHrP expression in collaboration with Gli2."