作为Hes7的下游标,Cdh2通过支持FGF信号传递来调节体体发生
Xueqi Jia1,2, Akihiro Isomura1,3,4,5, Ryoichiro Kageyama1,4
1RIKEN Center for Brain Science, Wako 351-0198, Japan.
概括
细分时钟中的HES7振荡控制了索米特的形成. 这项研究揭示了Cadherin-2 (Cdh2) 作为一个关键的Hes7目标基因,调节纤维细胞生长因子 (FGF) 信号,以维持Hes7振荡和适当的PSM分化时间.
科学领域:
- 发展生物学 发展生物学
- 基因规则 基因规则
- 细胞信号传递 细胞信号传递
背景情况:
- 细分时钟,涉及Hes7振荡在前皮层中皮层 (PSM),对于周期性somite形成至关重要.
- 细分时钟的完整调节基因网络的理解尚不完全.
研究的目的:
- 在细分时钟内识别Hes7的直接点基因.
- 阐明Hes7目标基因在调节Hes7振荡和PSM分化中的作用.
主要方法:
- 染色体免疫沉与测序 (ChIP-seq) 来识别Hes7的直接目标.
- 在小鼠胚胎干细胞中基因淘汰和过度表达.
- 诱导差异化进入PSM样组织,并对Hes7振荡进行实时成像.
主要成果:
- 卡德林-2 (Cdh2) 被确定为直接的Hes7标基因.
- Cdh2淘汰赛降低了纤维细胞生长因子 (FGF) 信号的调节,并导致过早的Hes7振荡停止.
- 过度表达Cdh2上调了FGF信号传递和延长了Hes7振荡.
- Hes7抑制了Cdh2mRNA,而Cdh2蛋白形成了一个后向前的梯度.
结论:
- 控制hes7的Cdh2是FGF信号的关键调节器.
- Hes7和Cdh2之间的相互作用维持了Hes7的振荡,决定了PSM分化的时间.
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