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A unique feature of vertebrate segmentation is its strict periodicity, which is governed by the segmentation clock consisting of numerous cellular oscillators. These cellular oscillators, driven by a negative-feedback loop of Hairy transcription factor, are linked through Notch-dependent intercellular coupling and display the synchronous expression of clock genes. Combining our transplantation experiments in zebrafish with mathematical simulations, we review how the cellular oscillators maintain synchrony and form a robust system that is resistant to the effects of developmental noise such as stochastic gene expression and active cell proliferation. The accumulated evidence indicates that the segmentation clock behaves as a "coupled oscillators," a mechanism that also underlies the synchronous flashing seen in fireflies., (Copyright 2007 Wiley-Liss, Inc.)

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.