Rice Ritva, Rice David P C, Thesleff Irma
Developmental Biology Programme, Institute of Biotechnology, University of Helsinki, Finland.
Dev Dyn. 2005 Jul;233(3):847-52. doi: 10.1002/dvdy.20430.
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.
颅骨和颅缝的发育受到复杂的调控，其中骨形态发生蛋白（Bmp）和成纤维细胞生长因子（Fgf）信号分别与Msx2/Twist和Noggin相互作用，调节额骨原基的增殖和颅缝融合。我们之前已经表明，有翼螺旋转录因子Foxc1是颅骨发育所必需的，它是Bmp对Msx2进行调控所必需的。我们现在表明，FGF2调节Foxc1的表达，这表明Foxc1整合了Bmp和Fgf信号通路。我们还表明，获得成骨潜能或成骨细胞分化不需要Foxc1。在Foxc1缺陷的颅骨间充质中，Fgf受体和Twist的表达正常，异位FGF2能够诱导骨桥蛋白的表达。此外，我们证明Foxc1不参与Noggin表达的调控。我们的研究结果表明，Foxc1独立于Twist或Noggin整合Bmp和Fgf信号通路。这个信号网络对于颅骨的正确模式形成和生长至关重要。
