The period of the somite segmentation clock is sensitive to Notch activity.
The period of the somite segmentation clock is sensitive to Notch activity.
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DOI：
10.1091/mbc.e11-02-0139
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发表时间：
2011-09
影响因子：
3.3
通讯作者：
Bessho Y
中科院分区：
文献类型：
--
作者：
Kim W;Matsui T;Yamao M;Ishibashi M;Tamada K;Takumi T;Kohno K;Oba S;Ishii S;Sakumura Y;Bessho Y
我们认为脊椎动物体分节时钟是发生在发育中的节律现象的一个例子。通过小鼠遗传学和数学分析，我们发现每个染色体前细胞的时钟周期对Notch活性很敏感。它可能是每个细胞适应其局部环境的系统。椎骨的数量严格限定于一个给定的物种，并取决于体的数量，体是在发育过程中形成的最早的同种结构。有时是由顺序分割形成的。体裂的周期性是由体前中胚层（PSM）中基因表达的同步振荡精心安排的，称为“体裂时钟”，其中Notch信号起着至关重要的作用。在这里，我们发现时钟周期对Notch活性很敏感，这是由其反馈调节器Notch调节的锚蛋白重复序列（narp）微调的，并且narp对于形成适当数量和形态的轴向骨架成分是必不可少的。narp的零突变小鼠椎骨较少，形态有缺陷。在nrp−/ -胚胎的PSM中，Notch活性增强，其中2-h的分割期延长了5分钟，从而形成更少的体及其形成的椎骨。Notch活性的降低在一定程度上挽救了体细胞数量上的nrp−/ -表型，但在形态上却没有。因此，我们认为体裂时钟的周期对Notch的活性很敏感，而nrap在椎骨和肋骨的形态中起着重要的作用。
We consider the vertebrate somite segmentation clock as an example of a rhythmic phenomenon that occurs in development. Using mouse genetics and mathematical analyses, we found that the period of the clock in each presomitic cell is sensitive to Notch activity. It may be a system for each cell to adapt to its local environment. The number of vertebrae is defined strictly for a given species and depends on the number of somites, which are the earliest metameric structures that form in development. Somites are formed by sequential segmentation. The periodicity of somite segmentation is orchestrated by the synchronous oscillation of gene expression in the presomitic mesoderm (PSM), termed the “somite segmentation clock,” in which Notch signaling plays a crucial role. Here we show that the clock period is sensitive to Notch activity, which is fine-tuned by its feedback regulator, Notch-regulated ankyrin repeat protein (Nrarp), and that Nrarp is essential for forming the proper number and morphology of axial skeleton components. Null-mutant mice for Nrarp have fewer vertebrae and have defective morphologies. Notch activity is enhanced in the PSM of the Nrarp−/– embryo, where the ∼2-h segmentation period is extended by 5 min, thereby forming fewer somites and their resultant vertebrae. Reduced Notch activity partially rescues the Nrarp−/– phenotype in the number of somites, but not in morphology. Therefore we propose that the period of the somite segmentation clock is sensitive to Notch activity and that Nrarp plays essential roles in the morphology of vertebrae and ribs.