Zhu Jie, Luz-Madrigal Agustin, Haynes Tracy, Zavada Julia, Burke Amy K, Del Rio-Tsonis Katia
Department of Biology, Miami University, Oxford, Ohio, United States of America.
PLoS One. 2014 Jul 8;9(7):e101748. doi: 10.1371/journal.pone.0101748. eCollection 2014.
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.
在本研究中，我们探讨了β-连环蛋白在介导雏鸡视网膜再生中的作用。雏鸡可通过激活眼部睫状体边缘（CM）中存在的干细胞/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（FGF2）。我们通过免疫组织化学观察到，损伤（视网膜切除术）后CM和RPE中核β-连环蛋白的动态变化。仅对损伤做出反应时，CM细胞中β-连环蛋白的核积累会短暂丧失，而只要有FGF2存在，核β-连环蛋白的丧失就会持续。然而，损伤后RPE中仍存在核β-连环蛋白阳性细胞，且这些细胞BrdU-/p27+，这表明核β-连环蛋白可阻止这些细胞进入细胞周期。如果存在FGF-2，RPE会发生去分化和增殖，同时核β-连环蛋白会丧失。此外，在视网膜切除术后，通过使用信号抑制剂（XAV939）破坏活性β-连环蛋白或过表达Lef-1的显性负性形式，可在没有FGF2的情况下诱导CM和RPE再生。我们的结果表明，β-连环蛋白可保护发育中的眼睛中的CM和RPE细胞不进入细胞周期，在损伤期间对RPE细胞尤其如此。因此，β-连环蛋白的失活是雏鸡视网膜再生的先决条件。
