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首页> 外文期刊>Nature >The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity
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The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity

机译：Mesp2转录因子通过抑制Notch活性建立节段边界

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摘要

The serially segmented ( metameric) structures of vertebrates are based on somites that are periodically formed during embryogenesis. A 'clock and wavefront' model has been proposed to explain the underlying mechanism of somite formation(1), in which the periodicity is generated by oscillation of Notch components ( the clock) in the posterior pre-somitic mesoderm (PSM)(2-6). This temporal periodicity is then translated into the segmental units in the 'wavefront'(7,8). The wavefront is thought to exist in the anterior PSM and progress backwards at a constant rate; however, there has been no direct evidence as to whether the levels of Notch activity really oscillate and how such oscillation is translated into a segmental pattern in the anterior PSM. Here, we have visualized endogenous levels of Notch1 activity in mice, showing that it oscillates in the posterior PSM but is arrested in the anterior PSM. Somite boundaries formed at the interface between Notch1-activated and - repressed domains. Genetic and biochemical studies indicate that this interface is generated by suppression of Notch activity by mesoderm posterior 2 (Mesp2) through induction of the lunatic fringe gene (Lfng). We propose that the oscillation of Notch activity is arrested and translated in the wavefront by Mesp2.
机译：脊椎动物的序列分段（同分异构）结构基于在胚胎发生过程中定期形成的体节。已经提出了一种``时钟和波前''模型来解释体节形成的潜在机制（1），其中周期性是由后声前中胚层（PSM）中的Notch分量（时钟）的振荡产生的周期性的（2- 6）。然后将该时间周期转换为“波前”（7,8）中的分段单位。波前被认为存在于PSM的前部，并以恒定的速率向后发展。但是，尚无关于Notch活动水平是否真正振荡以及这种振荡如何在前PSM中转化为节段性模式的直接证据。在这里，我们已经观察到小鼠中Notch1活性的内源性水平，表明它在后PSM中振荡，但在前PSM中被阻滞。 Somite边界在Notch1激活和受阻域之间的界面处形成。遗传和生化研究表明，该界面是由中胚层后壁2（Mesp2）通过诱导疯牛边缘基因（Lfng）抑制Notch活性而产生的。我们建议，Notch活动的振荡被Mesp2阻滞并在波前平移。

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