Building the spine: the vertebrate segmentation clock

One of the most striking characteristics of many animal and plant species is their organization in a series of periodically repeated anatomical modules. In animals, this particular patterning strategy of the body axis is termed segmentation, and it is observed in both vertebrates and invertebrates. Vertebrate segmentation has been associated with a molecular oscillator-the segmentation clock-whose existence had been predicted on theoretical grounds in the clock and wave-front model. The segmentation clock is proposed to generate pulses of signaling used for the positioning of segmental boundaries. Whereas several models have proposed that simple negative autoregulatory circuits involving the transcription repressors of the hairy and enhancer of split family constitute the clock pacemaker, recent microarray studies in mouse have identified a large network of oscillating signaling genes belonging to the Notch, Wnt, and FGF (fibroblast growth factor) pathways. Thus, significant progress has been made, but the molecular nature of the clockwork underlying the oscillator remains poorly understood. Few examples of oscillators exist in developmental biology, and the segmentation clock provides a unique model of periodic regulation in patterning.