由二进制编码指定的相变塑造了脊椎动物的眼杯。
Phase transition specified by a binary code patterns the vertebrate eye cup.
作者信息
Balasubramanian Revathi, Min Xuanyu, Quinn Peter M J, Giudice Quentin Lo, Tao Chenqi, Polanco Karina, Makrides Neoklis, Peregrin John, Bouaziz Michael, Mao Yingyu, Wang Qian, da Costa Bruna L, Buenaventura Diego, Wang Fen, Ma Liang, Tsang Stephen H, Fabre Pierre J, Zhang Xin
机构信息
Department of Ophthalmology, Columbia University, New York, NY, USA.
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
出版信息
Sci Adv. 2021 Nov 12;7(46):eabj9846. doi: 10.1126/sciadv.abj9846. Epub 2021 Nov 10.
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.
发育中的脊椎动物眼杯被分为神经视网膜（NR）、视网膜色素上皮（RPE）和睫状缘（CM）。通过单细胞分析，我们发现成纤维细胞生长因子（FGF）信号通路调节CM的自我更新、分化和存活等干细胞样特性，而这种特性由进化上保守的Wnt信号梯度平衡。FGF通过以不依赖糖原合成酶激酶3β（GSK3β）的方式稳定β-连环蛋白来促进CM中的Wnt信号通路。虽然Wnt信号通路根据FGF信号通路将NR转化为CM或RPE，但FGF根据Wnt活性将RPE转化为NR或CM。眼杯的默认命运是NR，但FGF和Wnt信号通路的协同作用在体内和人类视网膜类器官中均促进CM的形成。我们的研究表明，脊椎动物眼睛通过由FGF和Wnt信号通路组合编码决定的相变而发育。
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