PDF(Pubmed)
Abstract：
The skull roof, or calvaria, is comprised of interlocking plates of bones that encase the brain. Separating these bones are fibrous sutures that permit growth. Currently, we do not understand the instructions for directional growth of the calvaria, a process which is error-prone and can lead to skeletal deficiencies or premature suture fusion (craniosynostosis, CS). Here, we identify graded expression of fibronectin (FN1) in the mouse embryonic cranial mesenchyme (CM) that precedes the apical expansion of calvaria. Conditional deletion of Fn1 or Wasl leads to diminished frontal bone expansion by altering cell shape and focal actin enrichment, respectively, suggesting defective migration of calvarial progenitors. Interestingly, Fn1 mutants have premature fusion of coronal sutures. Consistently, syndromic forms of CS in humans exhibit dysregulated FN1 expression, and we also find FN1 expression altered in a mouse CS model of Apert syndrome. These data support a model of FN1 as a directional substrate for calvarial osteoblast migration that may be a common mechanism underlying many cranial disorders of disparate genetic etiologies.
摘要：
头骨屋顶，或者颅骨，由包裹大脑的互锁骨头组成。分离这些骨的是允许生长的纤维缝线。目前,我们不理解颅骨定向生长的指示，一个容易出错的过程，可能导致骨骼缺陷或过早的缝合融合(颅骨融合，CS）。这里,我们确定了在颅骨顶端扩张之前的小鼠胚胎颅间充质（CM）中纤连蛋白（FN1）的分级表达。Fn1或Wasl的条件缺失通过改变细胞形状和局灶性肌动蛋白富集导致额骨扩张减少，分别,提示颅骨祖细胞的迁移缺陷。有趣的是,Fn1突变体的冠状缝线过早融合。始终如一，人类CS的综合征形式表现出FN1表达失调，我们还发现在Apert综合征的小鼠CS模型中FN1表达发生了改变。这些数据支持FN1模型作为颅骨成骨细胞迁移的定向底物，这可能是许多不同遗传病因的颅骨疾病的共同机制。
