Foxc1 controls the growth of the murine frontal bone rudiment by direct regulation of a Bmp response threshold of Msx2

Development (Impact Factor: 6.46). 01/2013; 140(5). DOI: 10.1242/dev.085225
Source: PubMed


The mammalian skull vault consists of several intricately patterned bones that grow in close coordination. The growth of these bones depends on the precise regulation of the migration and differentiation of osteogenic cells from undifferentiated precursor cells located above the eye. Here, we demonstrate a role for Foxc1 in modulating the influence of Bmp signaling on the expression of Msx2 and the specification of these cells. Inactivation of Foxc1 results in a dramatic reduction in skull vault growth and causes an expansion of Msx2 expression and Bmp signaling into the area occupied by undifferentiated precursor cells. Foxc1 interacts directly with a Bmp responsive element in an enhancer upstream of Msx2, and acts to reduce the occupancy of P-Smad1/5/8. We propose that Foxc1 sets a threshold for the Bmp-dependent activation of Msx2, thus controlling the differentiation of osteogenic precursor cells and the rate and pattern of calvarial bone development.

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    • "nents of BMP signaling pathway candidate genes for such human congenital disease . A recent study showed that deficiency of Foxc1 or Fgf8 also causes bony syng - nathia in mice ( Inman et al . , 2013 ) . Foxc1 acts to reduce the phosphorylation level of Smad1 / 5 / 8 , and repress BMP - dependent gene expression in the osteogenic precursor cells ( Sun et al . , 2013 ) . Specifically in the jaw , Foxc1 deficiency leads to decreased Fgf8 expression in the oral ectoderm of the first pharyngeal arch . Mice carrying compound mutations in both Foxc1 and Fgf8 , or in Fgf8 alone exhibit bony syngnathia phenotype , indicating a genetic interaction between these two genes in jaw development ."
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