人类特异性NOTCH2NL基因影响痕信号和皮质神经发生
Ian T Fiddes1, Gerrald A Lodewijk2, Meghan Mooring1
1UC Santa Cruz Genomics Institute, Santa Cruz, CA, USA.
Cell
|June 2, 2018
概括
人类特有的NOTCH2NL基因增强了Notch信号,在进化过程中促进了大脑的大小. 它们的出现与基因组不稳定和神经发育障碍有关,
科学领域:
- 神经科学
- 进化生物学
- 遗传学
背景情况:
- 痕信号对于放射性质干细胞的增殖至关重要,并决定哺乳动物皮层中的神经元数量.
- 人类大脑在进化过程中扩大大小的遗传基础在很大程度上是未知的.
研究的目的:
- 研究人类特异性基因在新皮层扩张中的作用及其与神经发育障碍的潜在联系.
主要方法:
- 在放射性质中分析NOTCH2NL基因表达.
- 对NOTCH2NL等位基因进行功能研究,以评估它们对Notch信号的影响.
- 研究NOTCH2NL基因在1q21.1删除/重复综合征中的参与.
主要成果:
- 三种人类特有的NOTCH2NL对应物在放射性质中高度表达.
- NOTCH2NL等位基因差异性增强了诺奇信号,影响了神经元前代的分化.
- 宫外NOTCH2NL表达延迟了分化;NOTCH2NL删除加速了分化.
- NOTCH2NL基因位于1q21.1删除/重复综合征的断点,与大脑症,小脑症,自闭症和精神分裂症有关.
结论:
- 人类特有的NOTCH2NL基因可能有助于更大的人类新皮质的进化.
- 涉及NOTCH2NL的1q21.1位点的基因组不稳定性可能是复发性神经发育障碍的基础.
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