Foxc1 integrates Fgf and Bmp signalling independently of twist or noggin during calvarial bone development

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Abstract
Calvarial bone and suture development is under complex regulation where bone morphogenetic protein (Bmp) and fibroblast growth factor (Fgf) signalling interact with Msx2/Twist and Noggin and regulate frontal bone primordia proliferation and suture fusion, respectively. We have shown previously that the winged helix transcription factor Foxc1, which is necessary for calvarial bone development, is required for the Bmp regulation of Msx2. We now show that FGF2 regulates the expression of Foxc1, indicating that Foxc1 integrates Bmp and Fgf signalling pathways. We also show that Foxc1 is not needed for the acquisition of osteogenic potential or for the differentiation of osteoblasts. The expression of Fgf receptors and Twist were normal in Foxc1-deficient calvarial mesenchyme, and ectopic FGF2 was able to induce the expression Osteopontin. Furthermore, we demonstrate that Foxc1 does not participate in the regulation of Noggin expression. Our findings indicate that Foxc1 integrates the Bmp and Fgf signalling pathways independently of Twist or Noggin. This signalling network is essential for the correct patterning and growth of calvarial bones. Developmental Dynamics 233:847–852, 2005.