内部神经元规范的命运可塑性
Mohammed A Mostajo-Radji1,2,3, Walter R Mancia Leon1,4, Arnar Breevoort1,2
1The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
iScience
|April 23, 2025
概括
环境信号塑造神经元的身份. 鼠标中介性状突起的祖先产生了特定的皮质内神经元,而人类大脑有机体促进了有效的帕瓦胺阳性内神经元发育.
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:
- 哺乳动物中枢神经系统中的神经元亚型生成是由遗传程序控制的.
- 介质质突出 (MGE) 生成皮质内部神经元 (IN) 群体,具有不同的发育时间表.
- 外部信号对IN亚型认同的影响尚未完全理解,Pvalb阳性IN很难在体外建模.
研究的目的:
- 调查微环境线索对MGE衍生INs差异化的影响.
- 通过使用多种共同培养系统,探索Pvalb阳性IN发育体外建模的潜力.
- 为了确定Sst-阳性IN是否表现出命运可塑性,以响应特定的环境信号.
主要方法:
- 将老鼠MGE祖先移植到各种2D和3D共同培养系统中,包括老鼠和人类皮质,MGE和thalamic模型.
- 对Pvalb分化标记物,Sst特定标记物和围神经网络形成的分析.
- 在人类皮质模型上移植的Sst-阳性INs转移后的血统追踪.
主要成果:
- 三维人类皮质生成模型显著促进了Pvalb的分化和成熟.
- 这些模型导致了Sst标记物的下调,并形成了周神经网络.
- 血统追踪的Sst-阳性INs在暴露在人类皮质环境中时显示了Pvalb上调,表明命运可塑性.
结论:
- 微环境在塑造MGE衍生INs的身份方面发挥着至关重要的作用.
- 人类3D皮质生成模型为研究Pvalb阳性IN发育提供了一个有前途的平台.
- 来自MGE的IN表现出了显著的环境可塑性,挑战了固定发展轨迹的概念.
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