Horikawa Kazuki, Ishimatsu Kana, Yoshimoto Eiichi, Kondo Shigeru, Takeda Hiroyuki
Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Tokyo 113-0033, Japan.
Nature. 2006 Jun 8;441(7094):719-23. doi: 10.1038/nature04861.
Periodic somite segmentation in vertebrate embryos is controlled by the 'segmentation clock', which consists of numerous cellular oscillators. Although the properties of a single oscillator, driven by a hairy negative-feedback loop, have been investigated, the system-level properties of the segmentation clock remain largely unknown. To explore these characteristics, we have examined the response of a normally oscillating clock in zebrafish to experimental stimuli using in vivo mosaic experiments and mathematical simulation. We demonstrate that the segmentation clock behaves as a coupled oscillator, by showing that Notch-dependent intercellular communication, the activity of which is regulated by the internal hairy oscillator, couples neighbouring cells to facilitate synchronized oscillation. Furthermore, the oscillation phase of individual oscillators fluctuates due to developmental noise such as stochastic gene expression and active cell proliferation. The intercellular coupling was found to have a crucial role in minimizing the effects of this noise to maintain coherent oscillation.
脊椎动物胚胎中周期性体节的分割由“分割时钟”控制，该时钟由众多细胞振荡器组成。尽管由毛发负反馈回路驱动的单个振荡器的特性已得到研究，但分割时钟的系统级特性仍 largely 未知。为了探索这些特征，我们使用体内镶嵌实验和数学模拟研究了斑马鱼中正常振荡的时钟对实验刺激的反应。我们通过表明 Notch 依赖性细胞间通讯（其活性由内部毛发振荡器调节）将相邻细胞耦合以促进同步振荡，证明了分割时钟表现为耦合振荡器。此外，由于发育噪声，如随机基因表达和活跃的细胞增殖，单个振荡器的振荡相位会波动。发现细胞间耦合在最小化这种噪声的影响以维持相干振荡方面起着关键作用。
