Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA.
Development. 2013 Mar;140(5):1034-44. doi: 10.1242/dev.085225. Epub 2013 Jan 23.
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.
哺乳动物颅顶由几块错综复杂的图案化骨骼组成，这些骨骼生长密切协调。这些骨骼的生长取决于位于眼睛上方的未分化前体细胞中骨原细胞的迁移和分化的精确调节。在这里，我们证明了 Foxc1 在调节 Bmp 信号对 Msx2 的表达和这些细胞的特化的影响中的作用。Foxc1 的失活导致颅顶生长显著减少，并导致 Msx2 表达和 Bmp 信号扩张到未分化前体细胞占据的区域。Foxc1 直接与 Msx2 上游增强子中的 Bmp 反应元件相互作用，并作用于减少 P-Smad1/5/8 的占有率。我们提出 Foxc1 为 Bmp 依赖性 Msx2 激活设定了一个阈值，从而控制了成骨前体细胞的分化以及颅骨骨发育的速度和模式。
