The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity
The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity
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DOI：
10.1038/nature03591
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发表时间：
2005-05-19
期刊：
影响因子：
64.8
通讯作者：
Saga, Y
中科院分区：
文献类型：
--
作者：
Morimoto, M;Takahashi, Y;Saga, Y
脊椎动物的连续分节（位变异构）结构是基于在胚胎发育过程中周期性形成的体节。已经提出了一个“时钟和波前”模型来解释体节形成的潜在机制（1），其中周期性是由后部前体节中胚层（PSM）中Notch组件（时钟）的振荡产生的（2-6）。然后将这种时间周期性转换为“波前”中的分段单元（7，8）。波前被认为存在于前PSM中，并以恒定速率向后进展;然而，没有直接证据表明Notch活动水平是否真的振荡以及这种振荡如何转化为前PSM中的节段模式。在这里，我们已经可视化了小鼠内源性Notch 1活性水平，表明它在后PSM中振荡，但在前PSM中被阻止。体细胞边界形成在Notch 1激活和抑制域之间的接口。遗传和生物化学研究表明，这种界面是通过中胚层后2（Mesp 2）通过诱导疯狂边缘基因（Lfng）抑制Notch活性而产生的。我们提出Notch活性的振荡被Mesp 2捕获并在波前中平移。
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.