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

Self-assortment of progenitor cells is critical for establishing distinct tissue identities during development, including segregation of the optic cup into the neural retina (NR) and ciliary margin (CM). Although Wnt signaling is required for CM specification, here we show that genetic ablation of β-catenin in the peripheral optic cup does not prevent formation of the CM-derived ciliary body and iris in adult mice. Mosaic analysis reveals that β-catenin-deficient cells are excluded from the CM due to a Wnt-dependent switch from P- to N-cadherin. This cadherin switch drives segregation of otherwise similar cells into distinct clusters, as supported by theoretical modeling and experimental manipulation of cadherin interactions. Consequently, wild-type cells are preferentially retained in the CM niche to support ciliary body formation, a process reversed by deletion of P- and N-cadherins. Together, these findings demonstrate that Wnt signaling can define tissue niches through passive cell competition.