Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation.
Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation.
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DOI：
10.1016/j.ydbio.2008.03.028
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发表时间：
2008-06
影响因子：
2.7
通讯作者：
Haotian Zhao;Tianyu Yang;Bhavani P. Madakashira;C. Thiels;Chad A Bechtle;Claudia M. Garcia;Huiming Zhang-Huiming
中科院分区：
文献类型：
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作者：
Haotian Zhao;Tianyu Yang;Bhavani P. Madakashira;C. Thiels;Chad A Bechtle;Claudia M. Garcia;Huiming Zhang-Huiming
脊椎动物晶状体为研究调节终末分化的机制提供了一个很好的模型。尽管成纤维细胞生长因子（FGF）被认为是晶状体细胞分化的重要因素，但目前尚不清楚在晶状体发育的不同阶段，是哪些FGF受体介导了这些过程。在晶状体发育早期缺失三个FGF受体（Fgfr1 - 3）表明，仅表达Fgfr2或Fgfr3的单个等位基因就足以使晶状体发育正常，而仅拥有单个Fgfr1等位基因的小鼠则会患上白内障和小眼症。在缺少所有三个Fgfrs的晶状体中观察到深刻的缺陷。包括纤维细胞伸长不足，晶状体纤维细胞增生异常，细胞周期抑制剂p27kip1和p57kip2表达减少，细胞凋亡增加，Prox1、Pax6、c-Maf、E-cadherin和α-、β-和γ-晶体蛋白表达异常或减少。因此，虽然FGF受体的信号传导对晶状体纤维分化至关重要，但不同的FGF受体的功能是冗余的。
The vertebrate lens provides an excellent model to study the mechanisms that regulate terminal differentiation. Although fibroblast growth factors (FGFs) are thought to be important for lens cell differentiation, it is unclear which FGF receptors mediate these processes during different stages of lens development. Deletion of three FGF receptors (Fgfr1–3) early in lens development demonstrated that expression of only a single allele of Fgfr2 or Fgfr3 was sufficient for grossly normal lens development, while mice possessing only a single Fgfr1 allele developed cataracts and microphthalmia. Profound defects were observed in lenses lacking all three Fgfrs. These included lack of fiber cell elongation, abnormal proliferation in prospective lens fiber cells, reduced expression of the cell cycle inhibitors p27kip1and p57kip2, increased apoptosis and aberrant or reduced expression of Prox1, Pax6, c-Maf, E-cadherin and α-, β- and γ-crystallins. Therefore, while signaling by FGF receptors is essential for lens fiber differentiation, different FGF receptors function redundantly.