Abstract
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.
Highlights
The vertebrate eye develops through a series of co-ordinated interactions between tissues of different embryonic origin
By inactivating the b-catenin gene prior to the cellular commitment into prospective neural retinal cells and retinal pigment epithelium (RPE) cells in the optic vesicle, we have demonstrated that this gene is essential for optic cup formation. b-catenin has at least two different cellular functions; i) activating canonical Wnt signalling by translocation into the nucleus. ii) regulating cell adhesion by binding to the cadherin family of adhesion molecules [27]
We have shown that b-catenin mutant embryos have significantly down-regulated canonical Wnt signalling in the dorsal optic vesicle
Summary
The vertebrate eye develops through a series of co-ordinated interactions between tissues of different embryonic origin. The distal portion of the optic vesicle makes contact with the surface ectoderm which initiates the formation of the lens placode. Reciprocal interactions between the lens placode and the optic vesicle promote the formation of the optic cup [3]. Such inductive interactions might not be strictly necessary since it has been shown recently that the optic vesicle can form the optic cup by a self-organising mechanism that is independent of external cues from the lens placode [4]. Establishment of dorsoventral polarity and specification of the neural retina, retinal pigment epithelium (RPE) and optic stalk occurs concurrently with the transformation of the optic vesicle to optic cup [3]
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