Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.
PLoS One. 2013 Dec 4;8(12):e81158. doi: 10.1371/journal.pone.0081158. eCollection 2013.
A multitude of signalling pathways are involved in the process of forming an eye. Here we demonstrate that β-catenin is essential for eye development as inactivation of β-catenin prior to cellular specification in the optic vesicle caused anophthalmia in mice. By achieving this early and tissue-specific β-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/β-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 β-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 β-catenin-negative revealing that differentiation of the neural retinal cell classes is β-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, β-catenin is required for optic cup formation, commitment to RPE cells and maintenance of dorsal identity of the retina.
众多信号通路参与了眼睛形成的过程。在这里，我们证明β-catenin 对于眼睛发育是必不可少的，因为在视囊细胞特化之前使β-catenin失活会导致小鼠无眼。通过实现这种早期和组织特异性的β-catenin 失活，我们发现由于背侧视囊中经典 Wnt 信号的丢失，视网膜色素上皮 (RPE) 的决定被阻断，并且眼发育在视杯形成之前就被阻止。因此，这些结果表明 Wnt/β-catenin 信号通路在眼睛发育中的作用比以前的研究表明的更早，并且发挥了更核心的作用。在我们的遗传模型系统中，一些 RPE 细胞可以逃避β-catenin 的失活，导致小的视原基的形成。视原基包含几个被 RPE 包围的神经视网膜细胞类型。与 RPE 细胞不同，神经视网膜细胞可以是β-catenin 阴性的，这表明神经视网膜细胞类型的分化是β-catenin 非依赖性的。此外，尽管在突变的视囊中启动了背腹模式形成，但视原基中的神经视网膜细胞几乎只表现出腹侧特征。因此，β-catenin 对于视杯形成、RPE 细胞的决定以及视网膜背侧特征的维持是必需的。
