FEZ1通过调节神经元原生子群特异和迁移来参与人类胚胎大脑发育
Yinghua Qu1,2, Jonathan Jun-Yong Lim1,3,4, Omer An5
1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
iScience
|January 12, 2024
概括
人类结和延长蛋白zeta1 (FEZ1) 基因的突变会影响早期大脑发育. 删除FEZ1会破坏神经发育,影响细胞迁移和皮质层形成,导致神经发育障碍.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 人类结和延长蛋白zeta1 (FEZ1) 基因的突变与精神分裂症和雅各布森综合征有关.
- FEZ1在人类大脑发育中起作用,但其精确的功能尚未完全理解.
研究的目的:
- 通过使用人类大脑器官 (hCOs) 研究FEZ1在人类早期大脑发育中的作用.
- 了解FEZ1删除如何影响神经发育过程和基因表达.
主要方法:
- 利用人类大脑器官 (hCOs) 来建模早期大脑发育.
- 采用单细胞RNA测序来分析FEZ1-null hCOs中的基因表达和细胞群.
- 检查了细胞迁移和分化模式.
主要成果:
- FEZ1的表达在大脑发育的早期开始,存在于神经产生细胞和不成熟的神经元中.
- 删除FEZ1导致神经元和突触发育基因的表达受损.
- 观察到异常扩张的家庭主体仅蛋白质homeobox (HOPX) 负的外部辐射质细胞 (oRG) 和减少的HOPX阳性oRG,增加了HOPX负的oRG细胞流动性.
- 检测到异位子神经原生体局部化和中间原生体异常侵入深层神经元,表明皮质层形成缺陷.
结论:
- FEZ1对于正常的早期皮质大脑发育至关重要.
- FEZ1功能障碍通过破坏关键的发育过程,导致神经发育障碍.
相关概念视频
01:30Neurulation
41.9K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
41.9K
01:51Determination
18.5K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
18.5K