The segmentation clock: a molecular oscillator controlling the periodic arrangement of vertebrae

Olivier Pourquié
Department of Genetics
Harvard University

The spine is characterized by the periodic arrangement of vertebrae along the anterior-posterior (AP) axis. This segmental or metameric organization is established early in embryogenesis when pairs of embryonic segments called somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock . We demonstrated that the segmentation clock generates a complex signaling pulse of Notch, Wnt and FGF activity involved in the rhythmic production of somites. Our recent work argues that the segmentation clock behaves as an excitable system, thus providing a novel theoretical framework for understanding segmentation. In humans, mutations in genes associated with the function of the segmentation clock result in abnormal segmentation of the vertebral column suggesting that the segmentation clock also ticks in the human embryo. We have recently demonstrated that clock oscillations can be recapitulated and tracked in vitro in human iPS reporter cells differentiated to a PSM fate thus identifying the human segmentation clock. Our work largely contributed to impose vertebrate segmentation as a novel paradigm to study spatiotemporal regulation of signaling in development.  Our discoveries have had important consequences for the understanding of the patterning of the vertebrate embryonic axis and provided a conceptual framework to explain human spine malformations.