哺乳动物神经皮层神经元中基因调节网络的适应性进化
Zhuo Li1,2, Navjot Kaur1, Gabriel Santpere1,3
1Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.
bioRxiv : the preprint server for biology
|June 6, 2025
概括
研究人员确定ZBTB18是哺乳动物大脑进化的关键调节器,控制激发性神经元亚型和连接性. 它的破坏模仿了祖先的大脑特征,为神经发育障碍提供了洞察力.
科学领域:
- 神经科学是一个神经科学.
- 进化生物学 进化生物学
- 遗传学 是一个遗传学.
背景情况:
- 哺乳动物拥有复杂的大脑和多层新皮质,与他们的祖先不同.
- 这种复杂性源于各种刺激神经元 (ExN) 亚型和专门的投影系统.
- 这些特定于哺乳动物的大脑适应的进化驱动因素尚未完全理解.
研究的目的:
- 研究哺乳动物新皮层发育背后的进化机制.
- 为了确定特定的调节元素和基因对于哺乳动物大脑适应至关重要.
- 了解ZBTB18在激发性神经元身份和大脑连接中的作用.
主要方法:
- 在老鼠ExN亚型中对基因表达和cis-regulatory元素 (CREs) 的比较分析.
- 哺乳动物和非哺乳动物CREs的跨物种检查.
- 在小鼠刺激神经元中ZBTB18缺失的功能分析.
主要成果:
- 鉴定了由ZBTB18结合的特定哺乳动物CREs,与intratelencephalic (IT) 和 extratelencephalic (ET) 神经元亚型和连接性相关.
- ZBTB18及其向基因与智力障碍和自闭症有关.
- 在小鼠中Zbtb18删除改变了基因表达,减少了分子多样性,损害了皮质脊髓/状突出,增加了关联突出.
结论:
- ZBTB18是哺乳动物新皮层刺激神经元身份和连接的关键调节器.
- 由ZBTB18结合的哺乳动物特异性CREs对于这些适应是必不可少的.
- ZBTB18的失调会影响大脑发育和连接性,并对神经发育障碍产生影响.
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