R-Spondin 2通过建立FGF信号梯度来控制Xenopus的左右身体轴形成
Hyeyoon Lee1, Celine Marie Camuto1, Christof Niehrs2,3
1Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum (DKFZ), 69120, Heidelberg, Germany.
Nature communications
|February 2, 2024
概括
在胚胎中,向左流的液体流建立了身体轴对称性. 研究人员发现R-Spondin 2 (Rspo2) 作为一个信号,对抗FGF信号,促进左侧发育.
科学领域:
- 发育生物学是发展生物学.
- 胚胎学 胚胎学
- 细胞信号传递 细胞信号传递
背景情况:
- 脊椎动物的左右 (LR) 体轴形成取决于毛驱动的液体流在LR组织器 (LRO) 中.
- 这种流动破坏对称性并诱导左侧的机制仍然不完全理解.
- 之前的模型建议一种化学感应机制,涉及到向左作用的信号的丰富.
研究的目的:
- 为了识别涉及LR轴建立的难以捉摸的失控信号.
- 阐明状流动打破LR对称性的分子机制.
- 研究R-Spondin 2 (Rspo2) 在LR模式中的作用.
主要方法:
- 利用Xenopus胚胎作为一个模型系统.
- 研究了LRO中的R-Spondin 2 (Rspo2) 的表达和功能.
- 进行了Rspo2.2的功能增益和丧失实验.
- 分析了rspo2和fgf信号通路之间的相互作用,包括fgfr4和znrf3.
主要成果:
- 识别Rspo2作为一个对称表达的,sinistralizing信号下游的纤毛流.
- 证明Rspo2通过促进Fgfr4内细胞分裂来对抗FGF信号传递.
- 显示FGF信号是dextralizing,并在LRO形成梯度,这是由Rspo2.2调节的.
- Rspo2操纵破坏了FGF梯度,导致改变了LR模式.
结论:
- Rspo2的向左流产生FGF信号梯度,这对于打破LR对称性至关重要.
- Rspo2 作为一个关键的调解器,将机械流体流转为分子梯度,指定左侧发展.
- 这项研究揭示了LR模式的新机制,涉及RSpo2介导的FGF信号对抗.
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