Single-Cell-Resolution Imaging of the Impact of Notch Signaling and Mitosis on Segmentation Clock Dynamics
Single-Cell-Resolution Imaging of the Impact of Notch Signaling and Mitosis on Segmentation Clock Dynamics
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DOI：
10.1016/j.devcel.2012.09.009
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发表时间：
2012-11-13
影响因子：
11.8
通讯作者：
Amacher, Sharon L.
中科院分区：
文献类型：
--
作者：
Delaune, Emilie A.;Francois, Paul;Amacher, Sharon L.
脊椎动物的身体分割是由分割时钟控制的，分割时钟是一种分子振荡器，涉及早熟中胚层细胞中周期基因的转录振荡。事实证明，这种振荡系统的快速和高度动态的性质对单细胞水平的研究具有挑战性。我们在活着的胚胎中实现了以细胞水平的分辨率可视化时钟活动，从而可以直接比较相邻细胞的振荡。我们提供的直接证据表明，在斑马鱼Notch途径突变体中，分裂前中胚层细胞是异步振荡的。通过跟踪有丝分裂细胞的振荡，我们揭示了一个强大的细胞自主的、Notch不依赖的机制在有丝分裂后恢复振荡。最后，我们发现细胞在特定的振荡阶段优先分裂，这可能会减少细胞分裂在细胞同步中产生的噪音，并表明有丝分裂周期和时钟振荡之间存在有趣的关系。
Vertebrate body segmentation is controlled by the segmentation clock, a molecular oscillator involving transcriptional oscillations of cyclic genes in presomitic mesoderm cells. The rapid and highly dynamic nature of this oscillating system has proved challenging for study at the single-cell level. We achieved visualization of clock activity with a cellular level of resolution in living embryos, allowing direct comparison of oscillations in neighbor cells. We provide direct evidence that presomitic mesoderm cells oscillate asynchronously in zebrafish Notch pathway mutants. By tracking oscillations in mitotic cells, we reveal that a robust cell-autonomous, Notch-independent mechanism resumes oscillations after mitosis. Finally, we find that cells preferentially divide at a certain oscillation phase, likely reducing the noise generated by cell division in cell synchrony and suggesting an intriguing relationship between the mitotic cycle and clock oscillation.