在小鼠和人类神经模型中,c-JUN缺乏对乳头发育的影响
Jiantao Shi1, Qing Chen2, Jianheng Lai3
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Cell & bioscience
|December 20, 2024
概括
失去了c-Jun蛋白质会破坏神经纤维的延伸,并在胚胎早期造成 thalamus 发育缺陷. 这突显了c-Jun在神经系统发育和丘脑形成中的关键作用.
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
- 分子生物学分子生物学
背景情况:
- c-Jun是参与基因调节的关键转录因子.
- 它在哺乳动物的lamus等深层大脑结构的发展中的作用尚不清楚.
研究的目的:
- 研究c-Jun在神经系统早期发育中的功能.
- 为了确定c-Jun对丘脑形成和模式的影响.
主要方法:
- 使用c-Jun淘汰赛小鼠和衍生干细胞模型,包括神经前代细胞 (NPC),大脑器官 (COs) 和 thalamus器官 (ThOs).
- 采用组织学检查,免疫光染色,奥米克分析,以及功能损失/增益实验.
- 进行了染色体可访问性和RNA测序,以分析基因表达和调节.
主要成果:
- 6月份的淘汰赛小鼠显示脑纤维稀疏和泰拉木斯形.
- 缺少c-Jun加速了NPC诱导,但在神经细胞培养和有机体中损害了神经纤维延伸.
- 缺少c-Jun的thalamus有机体表现出缺陷的模式和减少的内部神经纤维.
- 在与 thalamus 相关的基因中,染色质可访问性降低了,c-Jun 过度表达拯救了缺陷.
- RNA-seq揭示了RSPO2和WNT8B等基因的显著下调,以及MSX1和LMX1B等基因的上调.
结论:
- c-Jun的枯竭会损害神经纤维的延伸,并在胚胎发育过程中导致 thalamus 发育不良.
- c-Jun对于适当的乳头/大脑发育至关重要,作为一个关键的转录调节器.
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