Shimojo Hiromi, Kageyama Ryoichiro
Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan; World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan; World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan; Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Kyoto University Graduate School of Biostudies, Kyoto 606-8501, Japan.
Semin Cell Dev Biol. 2016 Jan;49:76-82. doi: 10.1016/j.semcdb.2016.01.017. Epub 2016 Jan 24.
During somite segmentation, mRNA expression of the mouse Notch ligand Delta-like1 (Dll1) oscillates synchronously in the presomitic mesoderm (PSM). However, the dynamics of Dll1 protein expression were rather controversial, and their functional significance was not known. Recent live-imaging analysis showed that Dll1 protein expression also oscillates synchronously in the PSM. Interestingly, accelerated or delayed Dll1 expression by shortening or elongating the Dll1 gene, respectively, dampens or quenches Dll1 oscillation at intermediate levels, a phenomenon known as "amplitude/oscillation death" of coupled oscillators in mathematical modeling. Under this condition, oscillation of the Notch effector Hes7 is also dampened, leading to severe fusion of somites and their derivatives, such as vertebrae and ribs. Thus, the appropriate timing of Dll1 expression is critical for its oscillatory expression, pointing to the functional significance of Dll1-mediated oscillatory cell-cell interactions in the segmentation clock. In neural stem cells, Dll1 expression is also oscillatory, but non-synchronous, and when Dll1 oscillation is dampened, oscillation of another Notch effector, Hes1, is also dampened, leading to defects of neural development. In this review, we discuss the underlying mechanism for the different oscillatory dynamics (synchronous versus non-synchronous) in the PSM and neural stem cells in a unified manner.
在体节分割过程中，小鼠Notch配体Delta样1（Dll1）的mRNA表达在前体节中胚层（PSM）中同步振荡。然而，Dll1蛋白表达的动态变化颇具争议，其功能意义也尚不明确。最近的实时成像分析表明，Dll1蛋白表达在PSM中也同步振荡。有趣的是，分别通过缩短或延长Dll1基因来加速或延迟Dll1表达，会在中间水平抑制或消除Dll1振荡，这一现象在数学建模中被称为耦合振荡器的“振幅/振荡死亡”。在此条件下，Notch效应器Hes7的振荡也会受到抑制，导致体节及其衍生物（如椎骨和肋骨）严重融合。因此，Dll1表达的适当时间对其振荡表达至关重要，这表明Dll1介导的振荡性细胞间相互作用在分割时钟中具有功能意义。在神经干细胞中，Dll1表达也是振荡性的，但不同步，当Dll1振荡受到抑制时，另一个Notch效应器Hes1的振荡也会受到抑制，导致神经发育缺陷。在这篇综述中，我们以统一的方式讨论了PSM和神经干细胞中不同振荡动态（同步与不同步）的潜在机制。
