Canonical Wnt/β-Catenin Signalling Is Essential for Optic Cup Formation
Canonical Wnt/β-Catenin Signalling Is Essential for Optic Cup Formation
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DOI：
10.1371/journal.pone.0081158
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发表时间：
2013-12-04
期刊：
影响因子：
3.7
通讯作者：
Carlsson, Leif
中科院分区：
文献类型：
--
作者：
Hagglund, Anna-Carin;Berghard, Anna;Carlsson, Leif
在形成眼睛的过程中涉及多种信号通路。在这里，我们证明了-连环蛋白对眼睛发育至关重要，因为在视神经泡细胞分化之前-连环蛋白的失活导致了小鼠的眼肿。通过实现这种早期和组织特异性的β -连环蛋白失活，我们发现视网膜色素上皮（RPE）的承诺被阻断，并且由于视神经背囊中典型Wnt信号的丢失，在视神经杯形成之前眼睛发育被阻止。因此，这些结果表明，Wnt/ β -连环蛋白信号在眼睛发育中比以前的研究表明的更早被需要，并发挥更重要的作用。在我们的遗传模型系统中，一些RPE细胞可以逃脱β -连环蛋白失活，从而形成一个小的光学雏形。视神经基底包含几个被RPE包围的视网膜神经细胞类。与RPE细胞不同，神经视网膜细胞可能是β -连环蛋白阴性的，这表明神经视网膜细胞类别的分化与β -连环蛋白无关。此外，尽管背腹侧模式在突变的视神经囊泡中启动，视神经雏形中的视网膜细胞几乎完全显示出腹侧特征。因此，β -连环蛋白对于视杯的形成、RPE细胞的形成和视网膜背侧一致性的维持是必需的。
A multitude of signalling pathways are involved in the process of forming an eye. Here we demonstrate that beta-catenin is essential for eye development as inactivation of beta-catenin prior to cellular specification in the optic vesicle caused anophthalmia in mice. By achieving this early and tissue-specific beta-catenin inactivation we find that retinal pigment epithelium (RPE) commitment was blocked and eye development was arrested prior to optic cup formation due to a loss of canonical Wnt signalling in the dorsal optic vesicle. Thus, these results show that Wnt/beta-catenin signalling is required earlier and play a more central role in eye development than previous studies have indicated. In our genetic model system a few RPE cells could escape beta-catenin inactivation leading to the formation of a small optic rudiment. The optic rudiment contained several neural retinal cell classes surrounded by an RPE. Unlike the RPE cells, the neural retinal cells could be beta-catenin- negative revealing that differentiation of the neural retinal cell classes is beta-catenin-independent. Moreover, although dorsoventral patterning is initiated in the mutant optic vesicle, the neural retinal cells in the optic rudiment displayed almost exclusively ventral identity. Thus, beta-catenin is required for optic cup formation, commitment to RPE cells and maintenance of dorsal identity of the retina.