艾斯普姆淘汰揭示了控制大脑皮层大小的进化机制
Matthew B Johnson1,2, Xingshen Sun3,4,5, Andrew Kodani1,2
1Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Nature
|April 13, 2018
概括
中异常的状小头症相关 (ASPM) 基因损失导致小头症,揭示了它通过控制神经前代细胞行为来调节人类大脑大小和折叠的作用.
科学领域:
- 进化生物学
- 神经科学
- 遗传学
背景情况:
- 人类大脑皮质的特点是大尺寸和复杂的折叠 (化).
- 驱动皮层扩张的进化机制在很大程度上是未知的.
- 由于大脑结构和基因功能的特定物种差异,对小鼠的研究对人类皮质发育的洞察力有限.
研究的目的:
- 在调节大脑皮层大小和结构中研究异常的状小头症相关基因 (ASPM) 的进化作用.
- 了解ASPM在大脑发育中的作用的细胞机制.
- 探索ASPM的功能使用一个模型生物与一个状皮质和更接近的人类ASPM.
主要方法:
- 基因组编辑被用来创建 (Mustela putorius furo) 的Aspm基因的生殖系淘汰.
- 对ASPM淘汰的表型分析,重点是大脑重量,皮质表面积和厚度.
- 对胎儿皮发育的显微镜检查,特别是神经前细胞的行为和分布.
主要成果:
- Aspm淘汰表现出严重的小头症,大脑重量和皮质表面积显著减少,反映出人类的小头症.
- 观察到心室辐射质细胞过早移动到外腹区域的显著增加.
- 这些移位的细胞类似于外侧的放射性质细胞,这是一种与灵长类动物皮层扩张有关但在小鼠中不存在的祖先类型.
结论:
- ASPM在调节大脑皮层扩张方面发挥着关键作用,可能是通过控制放射性质细胞与心室表面的相互作用.
- 这种调节会调节不同神经前代细胞群之间的平衡,从而影响"皮质单元"的产生.
- 这些发现表明人类大脑大小的进化机制涉及ASPM对祖细胞动态的控制.
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