Ultradian Oscillators in Somite Segmentation and Other Biological Events

Somite formation occurs every 2 hours in mouse embryos by periodic segmentation of the anterior ends of the presomitic mesoderm, and this process is controlled by a biological clock called the segmentation clock. During this process, the basic helix-loop-helix gene Hes7 is cyclically expressed, and each cycle leads to generation of a bilateral pair of somites. Both sustained expression and loss of expression of Hes7 result in severe somite fusion, indicating that Hes7 constitutes an essential component of the segmentation clock. Interestingly, expression of the related gene Hes1 also oscillates with a periodicity of about 2 hours in many cell types. Both sustained Hes1 expression and loss of Hes1 activity lead to retardation of the G(1) phase of the cell cycle, suggesting that Hes1 oscillation with an ultradian rhythm is required for efficient cell proliferation. Both Hes1 and Hes7 oscillations are regulated by negative feedback and rapid degradation of their gene products. Strikingly, expression of other factors such as Stat-Socs and Smad signaling molecules also display ultradian rhythms. All of these data suggest that ultradian oscillations are more general responses than were previously thought and that oscillatory and sustained gene expression results in different biological outcomes.