Type 1 Fibroblast Growth Factor Receptor in Cranial Neural Crest Cell-derived Mesenchyme Is Required for Palatogenesis*
Type 1 Fibroblast Growth Factor Receptor in Cranial Neural Crest Cell-derived Mesenchyme Is Required for Palatogenesis*
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DOI：
10.1074/jbc.m113.463620
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Cong Wang;J. Y. F. Chang;Chaofeng Yang;Yanqing Huang;Junchen Liu;P. You;W. Mckeehan;Fen Wang
中科院分区：
文献类型：
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作者：
Cong Wang;J. Y. F. Chang;Chaofeng Yang;Yanqing Huang;Junchen Liu;P. You;W. Mckeehan;Fen Wang
背景：Fgfr1突变如何导致腭裂尚不清楚。结果：神经嵴细胞中Fgfr1基因的缺失导致腭裂的发生。结论：颅神经嵴（CNC）细胞中的FGFR1信号调控腭架生长和融合。意义：该发现首次证明了CNC细胞中FGF信号如何调节腭发生。腭裂是一种常见的先天性先天性缺陷。成纤维细胞生长因子（FGF）家族通过激活FGF受体酪氨酸激酶，在腭发育中发挥重要作用。Fgf或Fgfr突变与腭裂有关。迄今为止，大多数关于腭发育中FGF信号传导的机制研究都集中在上皮中的FGFR2上。尽管Fgfr1在颅神经嵴（CNC）衍生的腭裂间质中表达，并且Fgfr1突变与腭裂缺陷有关，但腭裂间质中的Fgfr1如何调节腭发育尚不清楚。在这里，我们报道了使用Wnt1Cre删除神经嵴细胞中的Fgfr1导致腭裂、唇裂和其他严重颅面缺陷。详细的分析显示Fgfr1的功能缺失突变并没有消除腭架中CNC细胞的模式。然而，它扰乱了额面区的细胞信号，延缓了上皮细胞和间质细胞的增殖，阻止了上腭架的升高，损害了上腭架的融合。这是第一个揭示CNC细胞中FGF信号如何调节腭发生的报告。
Background: How Fgfr1 mutations cause cleft palate is unclear. Results: Deleting Fgfr1 in neural crest cells caused defects in both palate shelf epithelium and mesenchyme and led to cleft palate. Conclusion: FGFR1 signaling in cranial neural crest (CNC) cells regulates palate shelf growth and fusion during palatogenesis. Significance: The finding for the first time demonstrates how FGF signaling in CNC cells regulates palatogenesis. Cleft palate is a common congenital birth defect. The fibroblast growth factor (FGF) family has been shown to be important for palatogenesis, which elicits the regulatory functions by activating the FGF receptor tyrosine kinase. Mutations in Fgf or Fgfr are associated with cleft palate. To date, most mechanistic studies on FGF signaling in palate development have focused on FGFR2 in the epithelium. Although Fgfr1 is expressed in the cranial neural crest (CNC)-derived palate mesenchyme and Fgfr1 mutations are associated with palate defects, how FGFR1 in palate mesenchyme regulates palatogenesis is not well understood. Here, we reported that by using Wnt1Cre to delete Fgfr1 in neural crest cells led to cleft palate, cleft lip, and other severe craniofacial defects. Detailed analyses revealed that loss-of-function mutations in Fgfr1 did not abrogate patterning of CNC cells in palate shelves. However, it upset cell signaling in the frontofacial areas, delayed cell proliferation in both epithelial and mesenchymal compartments, prevented palate shelf elevation, and compromised palate shelf fusion. This is the first report revealing how FGF signaling in CNC cells regulates palatogenesis.