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非神经内皮中的Claudin-3对于胚胎的神经折叠融合至关重要

Elizabeth-Ann Legere¹, Amanda I Baumholtz¹, Jean-François Boisclair Lachance²

¹Department of Human Genetics, McGill University, Canada; The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.

Developmental biology

|December 28, 2023

概括

克劳丁-3 (Cldn3) 蛋白对于胚胎的神经管闭合至关重要. 削弱Cldn3会通过影响神经折叠融合和顶端细胞表面完整性导致脊柱缺陷.

科学领域:

发展生物学发展生物学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

神经管的关闭对于胚胎发育至关重要,形成大脑和脊髓.
克劳丁是调节上皮细胞连接和透性的跨膜蛋白质.
以前的研究表明,克劳迪因与幼早期的神经管闭合有关.

研究的目的:

为了调查Claudin-3 (Cldn3) 在神经管闭合期间在非神经外皮中的特定作用.
了解Cldn3依赖的神经折叠融合背后的细胞机制.

主要方法:

在小胚胎中Cldn3的耗尽.
对神经管闭塞缺陷的分析,专注于脊髓神经管缺陷.
在非神经外皮细胞中检查顶端细胞表面形态和蛋白质定位 (Par3,Pals1).
评估F-actin信号在顶峰连接处的情况.

主要成果:

Cldn3的枯竭导致对叶酸不敏感的脊髓神经管缺陷,特别是神经折叠融合受损.
非神经性外皮细胞显示顶膜斑点增加和顶表面积减少.
保持了基极性,但Par3和Pals1的定位发生了变化.
在Cldn3-贫乏细胞的顶峰结处观察到减少的F-actin信号.

结论:

克劳丁-3在调节非神经外皮细胞顶端过程中起着至关重要的作用,这对于神经折叠融合至关重要.
通过确保神经管正确关闭,Cldn3是预防脊柱裂的关键因素.
这些发现为了解Cldn3对胚胎发育和先天性缺陷的贡献提供了一个细胞模型.

关键词:

肉肉肉肉克劳迪恩 (Claudin) 是一个很好的球员.细胞骨架细胞骨架神经管中的神经管.非神经性外皮外皮.表面的ectoderm是什么紧密的结口是紧密的结口.

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