Conservation of fibroblast growth factor function in lens regeneration
Conservation of fibroblast growth factor function in lens regeneration
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DOI：
10.1073/pnas.94.25.13701
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Tsonis, PA
中科院分区：
文献类型：
--
作者：
DelRioTsonis, K;Jung, JC;Tsonis, PA
在尾目两栖动物中，晶状体在发育和再生过程中的诱导通过不同的途径发生。在发育过程中，晶状体是由外胚层和视泡相互作用诱导的，而晶状体切除后，晶状体通过虹膜色素上皮细胞的转分化而再生。鉴于成纤维细胞生长因子(FGFs)在晶状体发育中的已知作用，我们研究了外源性成纤维细胞生长因子(FGFs)在晶状体再生过程中的表达和作用是否保守。在本文中，我们描述了成纤维细胞生长因子-1及其受体FGFR-2(KGFR和BEK变异体)和FGFR-3在晶体再生过程中的表达。这些基因在去分化的色素上皮细胞中有表达，在晶状体上皮细胞和分化纤维中表达水平较高，在视网膜中表达较低。这些表达模式提示FGFs参与了晶状体再生。为了进一步阐明这一功能，我们研究了外源性成纤维细胞生长因子-1和成纤维细胞生长因子-4在晶状体再生过程中的作用。在晶状体摘除的眼睛中，使用成纤维细胞生长因子-I或成纤维细胞生长因子-4的处理导致了类似于转基因小鼠晶状体发育过程中所引起的异常。影响包括上皮细胞向纤维细胞转化、双晶状体再生和晶状体极性异常。这些结果表明，尽管再生晶状体是由不同于晶状体发育过程中的机制诱导的，但在再生过程中，成纤维细胞生长因子分子是影响晶状体纤维分化、极性和形态发生的关键因素。从这个意义上讲，成纤维细胞生长因子在晶状体再生和发育中的作用应该被认为是保守的。这种保护应该有助于阐明尾龙晶状体再生的机制以及高等脊椎动物中没有晶状体再生的机制。
In urodele amphibians, lens induction during development and regeneration occurs through different pathways. During development, the lens is induced from the mutual interaction of the ectoderm and the optic vesicle, whereas after lentectomy the lens is regenerated through the transdifferentiation of the iris-pigmented epithelial cells. Given the known role of fibroblast growth factors (FGFs) during lens development, we examined whether or not the expression and the effects of exogenous FGF during urodele lens regeneration were conserved. In this paper, we describe expression of FGF-1 and its receptors, FGFR-2 (KGFR and bek variants) and FGFR-3, in newts during lens regeneration. Expression of these genes was readily observed in the dedifferentiating pigmented epithelial cells, and the levels of expression were high in the lens epithelium and the differentiating fibers and lower in the retina. These patterns of expression implied involvement of FGFs in lens regeneration. To further elucidate this function, we examined the effects of exogenous FGF-1 and FGF-4 during lens regeneration. FGF-I or FGF-4 treatment in lentectomized eyes resulted in the induction of abnormalities reminiscent to the ones induced during lens development in transgenic mice. Effects included transformation of epithelial cells to fiber cells, double lens regeneration, and lenses with abnormal polarity. These results establish that FGF molecules are key factors in fiber differentiation, polarity, and morphogenesis of the lens during regeneration even though the regenerating lens is induced by a different mechanism than in lens development. In this sense, FGF function in lens regeneration and development should be regarded as conserved. Such conservation should help elucidate the mechanisms of lens regeneration in urodeles and its absence in higher vertebrates.