CHD7与PBAF合作,控制多能神经形成
Ruchi Bajpai1, Denise A Chen, Alvaro Rada-Iglesias
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|February 5, 2010
概括
CHD7对神经 (NC) 细胞发育至关重要,对于形成面结构和神经系统至关重要. 在CHD7的突变导致CHARGE综合征,突出其在先天性异常和细胞迁移中的作用.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 查奇综合征是一种零星的,自体质的主导性疾病.
- 它的特点是多种先天性异常.
- 之前的假设表明神经异常,但仍然未经测试.
研究的目的:
- 研究CHD7在神经 (NC) 发育中的作用.
- 为了测试CHARGE综合征是异常NC发展造成的假设.
- 阐明CHD7在NC形成和迁移中的功能背后的分子机制.
主要方法:
- 在人类和Xenopus模型中研究CHD7功能.
- 在Xenopus胚胎中利用基因淘汰和过度表达技术.
- 在人类NC细胞中分析了CHD7与PBAF复合物的关联及其与调节元件 (SOX9增强剂,TWIST1上游元件) 的结合.
主要成果:
- CHD7对于多能迁移神经 (NC) 细胞的形成至关重要.
- 需要CHD7来激活关键的NC转录电路,包括Sox9,Twist和Slug.
- 在Xenopus中,Chd7的倒退重复了CHARGE综合征的特征.
- CHD7和PBAF合作调节NC基因表达和细胞迁移.
结论:
- CHD7在编排NC基因表达程序中起着保留的作用.
- 这项研究揭示了CHARGE综合征的病态胚胎学.
- CHD7的功能扩展到调节细胞运动,对更广泛的发育过程有影响.
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