He Fenglei, Soriano Philippe
Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Development. 2017 Nov 1;144(21):4026-4036. doi: 10.1242/dev.151068. Epub 2017 Sep 25.
Craniosynostosis is a prevalent human birth defect characterized by premature fusion of calvarial bones. In this study, we show that tight regulation of endogenous PDGFRα activity is required for normal calvarium development in the mouse and that dysregulated PDGFRα activity causes craniosynostosis. Constitutive activation of PDGFRα leads to expansion of cartilage underlying the coronal sutures, which contribute to suture closure through endochondral ossification, in a process regulated in part by PI3K/AKT signaling. Our results thus identify a novel mechanism underlying calvarial development in craniosynostosis.
颅缝早闭是一种常见的人类出生缺陷，其特征是颅骨过早融合。在本研究中，我们表明小鼠颅骨正常发育需要对内源性血小板衍生生长因子受体α（PDGFRα）活性进行严格调控，而PDGFRα活性失调会导致颅缝早闭。PDGFRα的组成性激活导致冠状缝下方软骨扩张，通过软骨内骨化促进缝线闭合，这一过程部分受PI3K/AKT信号通路调控。因此，我们的结果确定了颅缝早闭中颅骨发育的一种新机制。
