Department of Pathology, New York University School of Medicine, 550 1st Avenue, New York, NY 10016, USA.
Development. 2012 Apr;139(7):1346-58. doi: 10.1242/dev.076729.
The characterization of mesenchymal progenitors is central to understanding development, postnatal pathology and evolutionary adaptability. The precise identity of the mesenchymal precursors that generate the coronal suture, an important structural boundary in mammalian skull development, remains unclear. We show in mouse that coronal suture progenitors originate from hedgehog-responsive cephalic paraxial mesoderm (Mes) cells, which migrate rapidly to a supraorbital domain and establish a unidirectional lineage boundary with neural crest (NeuC) mesenchyme. Lineage tracing reveals clonal and stereotypical expansion of supraorbital mesenchymal cells to form the coronal suture between E11.0 and E13.5. We identify engrailed 1 (En1) as a necessary regulator of cell movement and NeuC/Mes lineage boundary positioning during coronal suture formation. In addition, we provide genetic evidence that En1 functions upstream of fibroblast growth factor receptor 2 (Fgfr2) in regulating early calvarial osteogenic differentiation, and postulate that it plays an additional role in precluding premature osteogenic conversion of the sutural mesenchyme.
中胚层祖细胞的特征对于理解发育、出生后病理学和进化适应性至关重要。产生冠状缝的中胚层前体细胞的确切身份仍然不清楚，冠状缝是哺乳动物头骨发育中的一个重要结构边界。我们在小鼠中表明，冠状缝祖细胞来源于 hedgehog 反应性颅侧轴旁中胚层（Mes）细胞，这些细胞迅速迁移到眶上区，并与神经嵴（NeuC）间充质建立单向谱系边界。谱系追踪显示，眶上间充质细胞的克隆和典型扩张形成了 E11.0 至 E13.5 之间的冠状缝。我们确定 engrailed 1（En1）是细胞运动和冠状缝形成过程中神经嵴/ Mes 谱系边界定位所必需的调节剂。此外，我们提供了遗传证据表明，En1 在调节早期颅骨成骨分化中，位于成纤维细胞生长因子受体 2（Fgfr2）的上游，并推测它在防止缝间充质过早成骨转化方面发挥了额外的作用。
