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

Revathi Balasubramanian, Xuanyu Min, Peter M.J. Quinn, Quentin Lo Giudice, Chenqi Tao, Karina Polanco, Neoklis Makrides, John Peregrin, Michael Bouaziz, Yingyu Mao, Qian Wang, Bruna L. da Costa, Diego Buenaventura, Fen Wang, Liang Ma, Stephen H. Tsang, Pierre J. Fabre, Xin Zhang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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 β-catenin in a GSK3β-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.

Original languageEnglish (US)
Article numbereabj9846
JournalScience advances
Issue number46
StatePublished - Nov 2021

ASJC Scopus subject areas

  • General


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