在神经细胞规范过程中,NuRD组件CHD3促进了BMP信号传递
Zoe H Mitchell1, Joery den Hoed2, Willemijn Claassen2
1Department of Life Sciences, Imperial College London, London, UK.
EMBO reports
|August 20, 2025
概括
在CHD3的致病变体导致Snijders Blok-Campeau综合征. 通过调节BMP信号传递,CHD3对神经细胞发育至关重要,其损失会损害面形成.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 斯尼德斯·布洛克-坎波综合征是一种神经发育障碍,与CHD3的遗传变异有关.
- 面异常是这种综合征的一个关键特征,表明CHD3在头部发育中的作用.
研究的目的:
- 研究CHD3在面发育中的功能.
- 阐明CHD3调节神经细胞 (CNCC) 规范的分子机制.
主要方法:
- 人类诱导的多能干细胞 (hiPSCs) 有或没有CHD3枯竭的分化为CNCCs.
- 对基因表达,染色质可访问性和信号通路活性 (BMP和Wnt) 的分析.
主要成果:
- 在早期的CNCC规范过程中,CHD3被上调,通过调节BMP响应元素的染色质可访问性来增强BMP信号传输.
- CHD3 枯竭导致抑制的 BMP 基因,减少染色体可访问性,以及 BMP 和 Wnt 信号之间的不平衡.
- 失去了CHD3功能导致失败的CNCC规范和异常的早期中皮体身份,通过调整Wnt信号水平,部分可逆.
结论:
- CHD3是BMP信号的关键调节者,对于正确的神经的规范和面发育至关重要.
- 这些发现为在Snijders Blok-Campeau综合征中观察到的面异常提供了分子基础.
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