Kageyama Ryoichiro, Masamizu Yoshito, Niwa Yasutaka
Institute for Virus Research, Kyoto University, and Japan Science and Technology Agency, CREST, Kyoto, Japan.
Dev Dyn. 2007 Jun;236(6):1403-9. doi: 10.1002/dvdy.21114.
Somites are formed by periodic segmentation of the presomitic mesoderm (PSM). This periodic event is controlled by the segmentation clock, where Notch signaling plays an essential role. The basic helix-loop-helix factor Hes7, a Notch effector, is cyclically expressed by negative feedback and regulates cyclic expression of Lunatic fringe (Lfng), a Notch modulator. Lfng then seems to periodically inhibit Notch, leading to oscillation in Notch activity. It is thought that these coupled negative feedback loops by Hes7 and Lfng are important for sustained and synchronized oscillations in the PSM. Of interest, another Notch effector, Hes1, is cyclically expressed by many cell types such as neuroblasts, suggesting that this clock is widely distributed and regulates many biological events. This review summarizes the recent finding about roles and mechanism of Notch signaling in the segmentation clock and discusses the significance of Hes1 oscillation in non-PSM cells.
体节由前体节中胚层（PSM）的周期性分割形成。这一周期性事件由分割时钟控制，其中Notch信号通路起着至关重要的作用。基本螺旋-环-螺旋因子Hes7是一种Notch效应因子，通过负反馈循环表达，并调节Notch调节剂Lunatic fringe（Lfng）的循环表达。然后Lfng似乎周期性地抑制Notch，导致Notch活性振荡。据认为，Hes7和Lfng的这些耦合负反馈环对于PSM中持续且同步的振荡很重要。有趣的是，另一种Notch效应因子Hes1在许多细胞类型如神经母细胞中循环表达，这表明该时钟广泛分布并调节许多生物学事件。本综述总结了关于Notch信号通路在分割时钟中的作用和机制的最新发现，并讨论了Hes1振荡在非PSM细胞中的意义。
