通过TFEB-PUMA轴对中枢神经系统髓的空间时间控制
Lu O Sun1, Sara B Mulinyawe1, Hannah Y Collins1
1Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|December 4, 2018
概括
转录因子EB (TFEB) 控制中枢神经系统 (CNS) 髓化时间. TFEB的损失导致过早的髓化,揭示了寡细胞发育和髓雕塑的关键分子机制.
科学领域:
- 神经科学
- 发育生物学
- 细胞生物学
背景情况:
- 神经系统的功能依赖于髓化以提供轴突隔离和支持.
- 调节中枢神经系统 (CNS) 髓化的精确空间和时间控制的分子机制尚未完全理解.
研究的目的:
- 确定控制中枢神经系统髓化的区域和时间特异性的分子机制.
- 阐明转录因子EB (TFEB) 在寡细胞发育和髓化中的作用.
主要方法:
- 研究了TFEB表达在分化的寡细胞.
- 在小鼠模型中分析了TFEB损失对髓化模式的影响.
- 检查了涉及PUMA和Bax-Bak激活的分子途径.
主要成果:
- 在分化寡细胞中,TFEB的表达很高.
- TFEB的损失导致大脑的早期和子宫外髓化.
- 通过PUMA和Bax-Bak,TFEB促进了前美林化寡干细胞的一个子集的细胞死亡.
- 这种机制是保守的,对控制髓化时间至关重要.
结论:
- TFEB以细胞自主作用调节寡细胞数量,并消除特定大脑区域的多余细胞.
- 这种TFEB介导的途径对于中枢神经系统髓化的时空特异性至关重要.
- 在神经系统发育过程中确定了一种新型的寡细胞内在机制.
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