Phase transition specified by a binary code patterns the vertebrate eye cup

The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE), and the ciliary margin (CM). By single-cell analysis, we showed that fibroblast growth factor (FGF) signaling regulates the CM in its stem cell-like property of self-renewal, differentiation, and survival, which is balanced by an evolutionarily conserved Wnt signaling gradient. FGF promotes Wnt signaling in the CM by stabilizing beta-catenin in a GSK3 beta-independent manner. While Wnt signaling converts the NR to either the CM or the RPE depending on FGF signaling, FGF transforms the RPE to the NR or CM dependent on Wnt activity. The default fate of the eye cup is the NR, but synergistic FGF and Wnt signaling promotes CM formation both in vivo and in human retinal organoid. Our study reveals that the vertebrate eye develops through phase transition determined by a combinatorial code of FGF and Wnt signaling.

Automated summary

The development of the vertebrate eye is determined by a combinatorial code of FGF and Wnt signaling, with FGF regulating the stem cell-like properties of the ciliary margin (CM) and Wnt maintaining a balance. FGF signaling promotes Wnt signaling in the CM through beta-catenin stabilization, while Wnt signaling converts the neural retina to either the CM or the retinal pigmented epithelium (RPE) depending on FGF signaling.