取决于Tbx6的Sox2调控决定了轴干细胞中的神经或中皮命运
Tatsuya Takemoto1, Masanori Uchikawa, Megumi Yoshida
1Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nature
|February 19, 2011
概括
在发育的胚胎中,Tbx6蛋白控制细胞命运决定. 它抑制Sox2基因活动,确保轴性干细胞发展成为神经组织而不是外轴性介质皮.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 分子遗传学 分子遗传学
背景情况:
- 经典模型提出的神经板发育仅来自ectoderm.
- 最近的研究揭示了神经板和轴性半皮体的常见双电位轴性干细胞.
- Tbx6无基因突变体表现出宫外神经管,这表明神经与大皮间命运选择中的作用.
研究的目的:
- 阐明Tbx6控制神经与中皮相对应命运选择的调节机制.
- 研究Tbx6在轴性干细胞分化过程中调节Sox2表达中的作用.
主要方法:
- 对Tbx6无突变小鼠胚胎的分析.
- 细胞谱系追踪实验. 细胞谱系追踪实验.
- 对Sox2及其增强剂N1.1.的基因表达分析.
- 在突变胚胎中通过CRISPR介导的增强剂-N1删除.
- 野生类型胚胎中Sox2转基因的错误表达.
主要成果:
- Tbx6通过增强剂N1活动抑制Sox2在发育的对轴性中皮.
- 在Tbx6突变体中,持久的增强剂N1活性导致宫外Sox2表达和神经管形成.
- 在Tbx6突变体中删除增强剂N1挽救了对轴间皮的发育.
- 这一过程中涉及到Wnt3a的Tbx6依赖性抑制.
结论:
- Tbx6是决定轴干细胞命运的关键调节器.
- Tbx6通过通过增强剂N1.1.抑制Sox2促进了对轴性中皮层的规范.
- 这种机制对于防止从中皮前体的异位神经发育至关重要.
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