Rice Ritva, Rice David P C, Olsen Bjorn R, Thesleff Irma
Developmental Biology Programme, Institute of Biotechnology, P.O. Box 56, 00014 University of Helsinki, Finland.
Dev Biol. 2003 Oct 1;262(1):75-87. doi: 10.1016/s0012-1606(03)00355-5.
Calvarial bones form by direct ossification of mesenchyme. This requires condensation of mesenchymal cells which then proliferate and differentiate into osteoblasts. Congenital hydrocephalus (ch) mutant mice lack the forkhead/winged helix transcription factor Foxc1. In ch mutant mice, calvarial bones remain rudimentary at the sites of initial osteogenic condensations. In this study, we have localized the ossification defect in ch mutants to the calvarial mesenchyme, which lacks the expression of transcription factors Msx2 and Alx4. This lack of expression is associated with a reduction in the proliferation of osteoprogenitor cells. We have previously shown that BMP induces Msx2 in calvarial mesenchyme (Development 125, 1241-1251, 1998). Here, we show that BMP also induces Alx4 in this tissue. We also show that BMP-induced expression of Msx2 and Alx4 requires Foxc1. We therefore suggest that Foxc1 regulates BMP-mediated osteoprogenitor proliferation and that this regulation is required for the progression of osteogenesis beyond the initial condensations in calvarial bone development.
颅盖骨通过间充质的直接骨化形成。这需要间充质细胞凝聚，然后增殖并分化为成骨细胞。先天性脑积水（ch）突变小鼠缺乏叉头/翼状螺旋转录因子Foxc1。在ch突变小鼠中，颅盖骨在最初的成骨凝聚部位仍发育不全。在本研究中，我们将ch突变体的骨化缺陷定位到颅盖间充质，其缺乏转录因子Msx2和Alx4的表达。这种表达缺失与骨祖细胞增殖减少有关。我们之前已经表明，骨形态发生蛋白（BMP）在颅盖间充质中诱导Msx2表达（《发育》125卷，1241 - 1251页，1998年）。在此，我们表明BMP也在该组织中诱导Alx4表达。我们还表明，BMP诱导的Msx2和Alx4表达需要Foxc1。因此，我们认为Foxc1调节BMP介导的骨祖细胞增殖，并且这种调节对于颅盖骨发育中初始凝聚之后的骨生成进展是必需的。
