2023年，浙江师范大学沈万华实验室在 International Journal of Molecular Sciences 发表研究，以爪蟾蝌蚪视顶盖（optic tectum）为模型，揭示了β-连环蛋白（β-catenin）与转录因子 SOX2 的协同作用在视觉经验依赖的神经干/祖细胞稳态维持中的关键角色。In 2023, the Shen WH lab (Zhejiang Normal University) published in Int J Mol Sci using the Xenopus tadpole optic tectum as a model, revealing how β-catenin and the transcription factor SOX2 cooperate to maintain visual-experience-dependent neural stem/progenitor cell (NSPC) homeostasis.
研究背景Background
视顶盖是爪蟾蝌蚪处理视觉信息的主要脑区，其神经元持续接受来自视网膜的输入。视顶盖中存在一类 SOX2 阳性的神经干/祖细胞群体，它们维持着局部神经发生的动态平衡。已知 Wnt/β-catenin 信号通路在多种发育系统中调控干细胞增殖与分化，但其在视觉经验依赖的视顶盖细胞稳态中的具体作用尚不清楚。The optic tectum is the main visual processing center in Xenopus tadpoles, continuously receiving retinal input. A SOX2-positive neural stem/progenitor cell (NSPC) population maintains local neurogenesis dynamics. Wnt/β-catenin signaling regulates stem cell proliferation and differentiation across many developmental contexts, but its role in visual experience-dependent tectal cell homeostasis was unclear.
主要研究方法Methods
- 视觉剥夺（visual deprivation）：将蝌蚪置于持续黑暗环境 4 天，阻断视网膜输入；Visual deprivation: housing tadpoles in continuous darkness for 4 days to block retinal input;
- 免疫荧光（Immunofluorescence）：定量分析视顶盖中 SOX2⁺ 细胞密度及增殖标记（BrdU/EdU）；Immunofluorescence: quantifying SOX2⁺ cell density and proliferative markers (BrdU/EdU) in the tectum;
- 吗啉环寡聚核苷酸（Morpholino）敲低 β-catenin 或 SOX2；Morpholino knockdown of β-catenin or SOX2;
- 共免疫沉淀（Co-IP）验证 β-catenin 与 SOX2 的蛋白互作；Co-immunoprecipitation (Co-IP) to validate β-catenin–SOX2 protein interaction;
- 体内单细胞电转染标记神经祖细胞谱系。In-vivo single-cell electroporation for neural progenitor lineage labeling.
关键结果Key results
- 视觉剥夺后，视顶盖 SOX2⁺ NSPC 数量显著减少，增殖速率降低，表明正常视觉输入是维持神经干/祖细胞稳态的必要条件；Visual deprivation significantly reduced SOX2⁺ NSPC numbers and proliferation rate, establishing that normal visual input is necessary for NSPC homeostasis;
- Morpholino 敲低 β-catenin 重现了视觉剥夺对 SOX2⁺ 细胞的影响，表明 Wnt/β-catenin 信号介导了视觉活动对 NSPC 的调控；β-catenin Morpholino knockdown phenocopied the deprivation-induced reduction in SOX2⁺ cells, indicating Wnt/β-catenin mediates visual activity–NSPC coupling;
- Co-IP 实验证实 β-catenin 与 SOX2 在视顶盖细胞中存在直接蛋白互作；Co-IP confirmed a direct β-catenin–SOX2 protein interaction in tectal cells;
- SOX2 敲低加重了 β-catenin 缺失对 NSPC 增殖的损伤，提示两者协同维持 NSPC 稳态。SOX2 knockdown exacerbated the proliferative defect of β-catenin-depleted NSPCs, suggesting cooperative maintenance of NSPC homeostasis.
科学意义Significance
该研究首次将视觉感觉经验与 Wnt/β-catenin–SOX2 分子轴联系起来，揭示了一条"视觉活动 → β-catenin 信号 → SOX2 表达 → NSPC 稳态"的分子调控链。这为理解感觉经验如何在细胞命运层面重塑发育中大脑提供了新视角，也为神经退行性疾病和脑损伤后神经再生研究提供了候选干预靶点。This work for the first time links visual sensory experience to the Wnt/β-catenin–SOX2 molecular axis, revealing a signaling chain: visual activity → β-catenin signaling → SOX2 expression → NSPC homeostasis. It provides new insight into how sensory experience shapes developing brain cell fate, and suggests candidate intervention targets for neurodegeneration and post-injury neural regeneration.
研究团队：高娟梅、陆一凡、罗一泓、段孝永、陈培轶、张旭旸、吴小虎、裘明秋、沈万华（浙江师范大学化学与生命科学学院）Authors: Gao JM, Lu YF, Luo YH, Duan XY, Chen PY, Zhang XY, Wu XH, Qiu MQ, Shen WH (Zhejiang Normal University)
参考文献References
- Gao JM, Lu YF, Luo YH, Duan XY, Chen PY, Zhang XY, Wu XH, Qiu MQ, Shen WH. (2023) β-catenin and SOX2 regulate visual experience-dependent cellular homeostasis in the developing Xenopus tectum. Int J Mol Sci 24(3):2785.
- He HY, Shen WH, Cline HT. (2011) Synaptic activity regulates neural proliferation in the optic tectum. Nat Neurosci 14(5):551–559.
- Logan CY & Nusse R. (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810.