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Determinative roles of FGF and Wnt signals in iris-derived lens regeneration in newt eye

机译：FGF和Wnt信号在虹膜源性虹膜晶状体再生中的决定性作用

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摘要

Total regeneration of experimentally excised lens from the dorsal part of the iris-pigmented epithelium of newts has been a key model of tissue regeneration via cells originating from a foreign tissue. Due to the strict spatial restriction of the lens origin in the newt iris, it has often been assumed that only the dorsal iris cells are endowed with an intrinsic potential to give rise to lens tissues. However, our reinvestigation of the process revealed completely different mechanisms underlying lens regeneration and its spatial restriction, comprising the following two steps: (i) Fibroblast growth factor (FGF) 2-dependent proliferation of iris-pigmented epithelium and activation of early lens genes (Pax6, Sox2, MafB) over the entire circumference of the iris; and (ii) dorsal iris-restricted activation of the canonical Wnt signals (involving Wnt2b and Frizzeld4) that leads to localized expression of late lens genes (Prox1, Sox1, beta-crystallin). Injection of FGF2 into normal eyes specifically elicited the second lens development from the dorsal iris, and the administration of recombinant Wnt3a to the cultured iris-pigmented epithelium caused even ventral iris-derived lens development. Thus, it is concluded that the regulation of FGF2 and Wnt signals is a determinative of the iris-derived lens regeneration in the newt eye.
机译：从虹膜色素沉着的of上皮的背侧部分完全切除实验切除的晶状体已成为通过异源组织细胞再生组织的关键模型。由于the虹膜中晶状体起源的严格空间限制，通常认为只有背虹膜细胞才具有产生晶状体组织的内在潜力。然而，我们对该过程的重新调查揭示了晶状体再生及其空间限制的完全不同的机制，包括以下两个步骤：（i）成纤维细胞生长因子（FGF）2依赖性虹膜色素上皮细胞的增殖和早期晶状体基因的激活（ Pax6，Sox2，MafB）在虹膜的整个圆周上; （ii）规范性Wnt信号（涉及Wnt2b和Frizzeld4）的背虹膜受限激活，导致晚期晶状体基因（Prox1，Sox1，β-crystallin）的局部表达。将FGF2注入正常眼中会特异性地引起从背侧虹膜开始的第二个晶状体发育，并且向培养的虹膜色素上皮施用重组Wnt3a甚至会导致腹侧虹膜衍生的晶状体发育。因此，可以得出结论，FGF2和Wnt信号的调节是the眼睛中虹膜来源的晶状体再生的决定因素。

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