Coupling cellular oscillators: a mechanism that maintains synchrony against developmental noise in the segmentation clock.

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.