Morimoto Mitsuru, Takahashi Yu, Endo Maho, Saga Yumiko
Division of Mammalian Development, National Institute of Genetics, Mishima, Japan.
Nature. 2005 May 19;435(7040):354-9. doi: 10.1038/nature03591.
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, in which the periodicity is generated by oscillation of Notch components (the clock) in the posterior pre-somitic mesoderm (PSM). This temporal periodicity is then translated into the segmental units in the 'wavefront'. 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.
脊椎动物的系列分段（分节）结构基于胚胎发育过程中周期性形成的体节。已提出一种“时钟和波前”模型来解释体节形成的潜在机制，其中周期性由后体节中胚层（PSM）中Notch成分（时钟）的振荡产生。然后这种时间周期性在“波前”中转化为节段单元。波前被认为存在于前PSM中并以恒定速率向后推进；然而，关于Notch活性水平是否真的振荡以及这种振荡如何在前PSM中转化为节段模式，尚无直接证据。在这里，我们可视化了小鼠体内Notch1活性的内源性水平，表明它在后PSM中振荡但在前PSM中停止。体节边界在Notch1激活和抑制区域之间的界面处形成。遗传和生化研究表明，这种界面是由中胚层后部2（Mesp2）通过诱导lunatic fringe基因（Lfng）抑制Notch活性而产生的。我们提出Notch活性的振荡通过Mesp2在前波前中停止并转化。
