机械传感器YAP通过TEAD4-LEF1转录连接器协调人类神经形形成
Jinghao Hu1, Zan He1, Huifang Hu2
1Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.
Science China. Life sciences
|December 1, 2025
概括
机械信号指导神经管的发育. 河马的路径 河马的路径
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 机械生物学 机械生物学
背景情况:
- 机械信号对人类神经管形态发生至关重要,但人们对其了解甚少.
- 河马通路,特别是YAP,与机械传导有关.
研究的目的:
- 阐明YAP如何在神经管发育过程中将机械线索转化为转录程序.
- 为了研究 YAP-LEF1 轴在神经红形态发生过程中的作用.
主要方法:
- 利用人类皮质器官来研究神经管发育.
- 研究了YAP在不同机械张力下的局部化和功能.
- 评估了YAP和LEF1操纵对上皮质极性和红形成的影响.
主要成果:
- 在神经红中,YAP局部化到高压的顶端域.
- YAP的枯竭破坏了上皮质极性,细胞骨,紧的结节和纤毛发生,损害了罗塞特形态发生.
- YAP-TEAD4复合体激活了LEF1,一个Wnt信号调节器.
- LEF1缺乏模仿了YAP损失,而LEF1过度表达部分挽救了缺陷.
结论:
- YAP-LEF1轴集成神经管发育中的机械和形态遗传信号.
- 这个轴对于正确的神经形形成至关重要.
- YAP-LEF1通路为神经管缺陷 (如无脑症) 提供了潜在的治疗标.
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