β-Catenin inactivation is a pre-requisite for chick retina regeneration.

β-Catenin inactivation is a pre-requisite for chick retina regeneration.
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β-catenin灭活是鸡视网膜再生的先决条件。

DOI:
10.1371/journal.pone.0101748
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Del Rio-Tsonis K
Del Rio-Tsonis K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhu J;Luz-Madrigal A;Haynes T;Zavada J;Burke AK;Del Rio-Tsonis K

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在本研究中,我们探讨了β-catenin在介导鸡视网膜再生中的作用。小鸡可以通过激活存在于眼睛睫状缘(CM)中的干细胞/祖细胞或通过视网膜色素上皮(RPE)的转分化来再生其视网膜。这两种模式都需要成纤维细胞生长因子2(FGF 2)。采用免疫组织化学方法观察视网膜损伤后CM和RPE细胞核β-catenin的动态变化。在单独的损伤反应中,CM细胞中的β-连环蛋白核积累短暂丢失,而只要存在FGF 2,核β-连环蛋白的丢失就保持不变。然而,核β-catenin阳性细胞响应于损伤而保留在RPE中,并且是BrdU-/p27+,表明核β-catenin阻止这些细胞进入细胞周期。如果存在FGF 2,则RPE经历去分化和增殖,伴随着核β-连环蛋白的损失。此外,视网膜切除术后通过使用信号传导抑制剂(XAV 939)或过表达Lef-1的显性负性形式破坏活性β-连环蛋白诱导在不存在FGF 2的情况下从CM和RPE再生。我们的研究结果表明,β-连环蛋白保护CM和RPE细胞进入发育中的眼睛的细胞周期,特别是在损伤期间的RPE。因此,β-连环蛋白的失活是鸡视网膜再生的先决条件。
In the present study we explored the role of β-catenin in mediating chick retina regeneration. The chick can regenerate its retina by activating stem/progenitor cells present in the ciliary margin (CM) of the eye or via transdifferentiation of the retinal pigmented epithelium (RPE). Both modes require fibroblast growth factor 2 (FGF2). We observed, by immunohistochemistry, dynamic changes of nuclear β-catenin in the CM and RPE after injury (retinectomy). β-catenin nuclear accumulation was transiently lost in cells of the CM in response to injury alone, while the loss of nuclear β-catenin was maintained as long as FGF2 was present. However, nuclear β-catenin positive cells remained in the RPE in response to injury and were BrdU-/p27+, suggesting that nuclear β-catenin prevents those cells from entering the cell cycle. If FGF2 is present, the RPE undergoes dedifferentiation and proliferation concomitant with loss of nuclear β-catenin. Moreover, retinectomy followed by disruption of active β-catenin by using a signaling inhibitor (XAV939) or over-expressing a dominant negative form of Lef-1 induces regeneration from both the CM and RPE in the absence of FGF2. Our results imply that β-catenin protects cells of the CM and RPE from entering the cell cycle in the developing eye, and specifically for the RPE during injury. Thus inactivation of β-catenin is a pre-requisite for chick retina regeneration.
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