Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells.
Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells.
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DOI：
10.1186/s12915-014-0063-7
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发表时间：
2014-08-13
期刊：
影响因子：
5.4
通讯作者：
Martinez Arias A
中科院分区：
文献类型：
--
作者：
Turner DA;Rué P;Mackenzie JP;Davies E;Martinez Arias A
原条的形成是原肠胚形成的第一个可见迹象，原肠胚形成是在早期发育期间由单个上皮形成三个胚层的过程。胚胎干细胞（ESC）为理解与这些过程相关的分子和细胞事件提供了一个很好的系统。先前在胚胎和培养物中的工作已经显示了来自结/TGFβR和Wnt/β-连环蛋白信号传导途径的会聚信号如何指定细胞采用连续条纹样命运并指导它们进行上皮向间充质转化（EMT）。然而，这些方法中的许多依赖于遗传分析，而没有考虑单细胞内事件的时间进展。此外，目前还不清楚胚胎中的事件在多大程度上能够在培养中复制。在这里，我们结合联合收割机流式细胞术和定量活单细胞成像方法，以证明如何控制小鼠胚胎干细胞向一个原始条纹的命运在文化中的结果显示在早期小鼠发育过程中观察到的许多特征，包括短暂的短尾表达，EMT和运动性增加的细胞分化。我们还发现，EMT启动了这一过程，这是由brachyury的作用，其表达依赖于EMT和β-catenin活性的燃料和终止。作为我们分析的结果，我们提出，brachyury表达的主要输出是在控制的速度的细胞是过境的原始条纹。本文的在线版本（doi：10.1186/s12915-014-0063-7）包含补充材料，可供授权用户使用。
The formation of the primitive streak is the first visible sign of gastrulation, the process by which the three germ layers are formed from a single epithelium during early development. Embryonic stem cells (ESCs) provide a good system for understanding the molecular and cellular events associated with these processes. Previous work, both in embryos and in culture, has shown how converging signals from both nodal/TGFβR and Wnt/β-catenin signalling pathways specify cells to adopt a primitive-streak-like fate and direct them to undertake an epithelial-to-mesenchymal transition (EMT). However, many of these approaches have relied on genetic analyses without taking into account the temporal progression of events within single cells. In addition, it is still unclear to what extent events in the embryo are able to be reproduced in culture. Here, we combine flow cytometry and a quantitative live single-cell imaging approach to demonstrate how the controlled differentiation of mouse ESCs towards a primitive streak fate in culture results in cells displaying many of the characteristics observed during early mouse development including transient brachyury expression, EMT and increased motility. We also find that the EMT initiates the process, and this is both fuelled and terminated by the action of brachyury, whose expression is dependent on the EMT and β-catenin activity. As a consequence of our analysis, we propose that a major output of brachyury expression is in controlling the velocity of the cells that are transiting out of the primitive streak. The online version of this article (doi:10.1186/s12915-014-0063-7) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Evans AL;Faial T;Gilchrist MJ;Down T;Vallier L;Pedersen RA;Wardle FC;Smith JC
通讯作者：
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影响因子：
2.7
作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.6
作者：
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通讯作者：
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DOI：
10.1242/dev.014357
发表时间：
2008-02
期刊：
Development (Cambridge, England)
影响因子：
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作者：
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通讯作者：
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