在大脑发育过程中,HDAC1和HDAC2调节Wnt信号,以调节神经前代过渡
Yue Zhu1, Yunyun Huang1, Tianxiang Tang1
1Department of Anesthesia, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, and Zhongshan Hospital, Fudan University, Shanghai 200032, China.
iScience
|September 3, 2024
概括
基因组脱乙酶1和2 (HDAC1/2) 通过抑制Wnt信号来控制神经发生,这对于在皮层发育过程中从神经上皮质原体过渡到放射性质原体至关重要.
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
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 精确的神经生成对于皮质的发育和功能至关重要.
- 神经发生的缺陷与神经发育障碍有关.
- 调节从神经上皮原体 (NP) 转变为放射性质原体 (RGP) 的机制尚未完全理解.
研究的目的:
- 为了研究基因组脱乙酶1和2 (HDAC1/2) 在NP-RGP过渡中的作用.
- 阐明Wnt信号在这个关键的发育过程中的参与.
- 为了识别控制新皮质祖先命运的表观遗传调节者.
主要方法:
- 在NP中HDAC1/2的有条件耗尽.
- 对Wnt信号基因表达的分析.
- 多组学分析 (基因组学,转录组学,表观组学).
- 在体内,Wnt9a过度表达和Wnt抑制剂的使用.
主要成果:
- HDAC1/2 枯竭调节了 Wnt 信号基因,阻碍了从 NP 到 RGP 的过渡.
- 过渡障碍导致新皮层的形形成.
- 确定HDAC1/2对于降低Wnt信号的调节至关重要,其中Wnt9a是关键目标.
- 过度表达Wnt9a增加了NP种群,并破坏了皮质组织.
- 由于Wnt的抑制,部分地挽救了观察到的皮质缺陷.
结论:
- 通过HDAC1/2介导的Wnt信号的抑制对于NP到RGP的过渡至关重要.
- 通过HDAC1/2对Wnt信号的表观遗传调节对于正确的新皮层发育至关重要.
- 这种途径的失调会导致神经发育异常.
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