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

doi:10.1126/sciadv.abj9846

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

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Abstract

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 language	English (US)
Article number	eabj9846
Journal	Science advances
Volume	7
Issue number	46
DOIs	https://doi.org/10.1126/sciadv.abj9846
State	Published - Nov 2021

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Balasubramanian, R., Min, X., Quinn, P. M. J., Giudice, Q. L., Tao, C., Polanco, K., Makrides, N., Peregrin, J., Bouaziz, M., Mao, Y., Wang, Q., da Costa, B. L., Buenaventura, D., Wang, F., Ma, L., Tsang, S. H., Fabre, P. J., & Zhang, X. (2021). Phase transition specified by a binary code patterns the vertebrate eye cup. Science advances, 7(46), [eabj9846]. https://doi.org/10.1126/sciadv.abj9846

Balasubramanian, R, Min, X, Quinn, PMJ, Giudice, QL, Tao, C, Polanco, K, Makrides, N, Peregrin, J, Bouaziz, M, Mao, Y, Wang, Q, da Costa, BL, Buenaventura, D, Wang, F, Ma, L, Tsang, SH, Fabre, PJ & Zhang, X 2021, 'Phase transition specified by a binary code patterns the vertebrate eye cup', Science advances, vol. 7, no. 46, eabj9846. https://doi.org/10.1126/sciadv.abj9846

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title = "Phase transition specified by a binary code patterns the vertebrate eye cup",

abstract = "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.",

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

note = "Funding Information: This work was supported by a grant from the NIH (EY025933 to X.Z.). The Columbia Ophthalmology Core Facility is supported by NIH Core grant 5P30EY019007 and unrestricted funds from Research to Prevent Blindness (RPB). R.B. is a recipient of Knights Templar Eye Foundation Career Starter grant and Bright Focus Foundation National Glaucoma Research. P.M.J.Q. is a recipient of Curing Retinal Blindness Foundation grant and Knights Templar Eye Foundation Career Starter grant. B.L.d.C. is a recipient of a Capes PhD scholarship. P.J.F. and Q.L.G. were supported by funds from the Swiss National Fund (Ambizione grant PZ00P3_174032 to P.J.F.). Q.W. is a recipient of Postdoctoral Fellowship from Natural Sciences and Engineering Research Council of Canada. C.T. is a recipient of a Jonas Scholar award. S.H.T. is supported by Jonas Children's Vision Care. X.Z. is supported by Jules and Doris Stein Research to Prevent Blindness Professorship. Jonas Children's Vision Care receives the support of U01 EY030580, U54OD020351, R24EY028758, R24EY027285, 5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R01EY031354, and R21AG050437. Publisher Copyright: {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",

year = "2021",

month = nov,

doi = "10.1126/sciadv.abj9846",

language = "English (US)",

volume = "7",

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T1 - Phase transition specified by a binary code patterns the vertebrate eye cup

AU - Balasubramanian, Revathi

AU - Min, Xuanyu

AU - Quinn, Peter M.J.

AU - Giudice, Quentin Lo

AU - Tao, Chenqi

AU - Polanco, Karina

AU - Makrides, Neoklis

AU - Peregrin, John

AU - Bouaziz, Michael

AU - Mao, Yingyu

AU - Wang, Qian

AU - da Costa, Bruna L.

AU - Buenaventura, Diego

AU - Wang, Fen

AU - Ma, Liang

AU - Tsang, Stephen H.

AU - Fabre, Pierre J.

AU - Zhang, Xin

N1 - Funding Information: This work was supported by a grant from the NIH (EY025933 to X.Z.). The Columbia Ophthalmology Core Facility is supported by NIH Core grant 5P30EY019007 and unrestricted funds from Research to Prevent Blindness (RPB). R.B. is a recipient of Knights Templar Eye Foundation Career Starter grant and Bright Focus Foundation National Glaucoma Research. P.M.J.Q. is a recipient of Curing Retinal Blindness Foundation grant and Knights Templar Eye Foundation Career Starter grant. B.L.d.C. is a recipient of a Capes PhD scholarship. P.J.F. and Q.L.G. were supported by funds from the Swiss National Fund (Ambizione grant PZ00P3_174032 to P.J.F.). Q.W. is a recipient of Postdoctoral Fellowship from Natural Sciences and Engineering Research Council of Canada. C.T. is a recipient of a Jonas Scholar award. S.H.T. is supported by Jonas Children's Vision Care. X.Z. is supported by Jules and Doris Stein Research to Prevent Blindness Professorship. Jonas Children's Vision Care receives the support of U01 EY030580, U54OD020351, R24EY028758, R24EY027285, 5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R01EY031354, and R21AG050437. Publisher Copyright: © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

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

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