Wnt signaling regulates passive cell competition in the retina by inducing differential cell adhesion

Abstract Self-assortation of progenitor cells during development is essential for establishment of distinct tissue identity. This is exemplified in the eye, where the early optic cup is divided into the neural retina (NR) in the center and the ciliary margin (CM) in the periphery. Previous studies have demonstrated that Wnt signaling is required for specification of the CM, but here we show that genetic ablation of Wnt signaling mediator β-catenin in the peripheral optic cup failed to prevent the formation of the CM-derived ciliary body and iris in adult animals. Mosaic analysis revealed that this was only partially due to loss of adherens junctions among β-catenin deficient cells, which were preferentially excluded from the CM. Even in β-catenin mutant cells that can maintain adherens junctions, their inability to mediate Wnt signaling resulted in a change from P-cadherin to N-cadherin expression. We showed that this cadherin switch was sufficient to segregate otherwise identical cells into separate clusters. As a result, the ciliary body and iris were still formed after inactivation of Wnt signaling in the peripheral retina. These results showed that the dual functions of β-catenin in adherens junction and Wnt signaling are required for the passive cell competition to constitute retinal compartments.