Tissue-wide, synchronous Erk oscillations time the segmentation of the zebrafish notochord

The generation of a periodic body plan is a fundamental property of vertebrates. While biological oscillators provide a mechanism for timing the formation of repeated structures, few examples of signaling oscillators have been identified in development. Here, we show that the addition of repeating mineralizing segments in the zebrafish notochord is timed by tissue-wide, synchronous oscillations of Erk activity. The oscillations are mediated by delayed negative feedback from spry and dusp and expression of the Egf ligand. The uniform increase in egf expression controls the emergence of the oscillations, revealing the mechanism controlling the onset of notochord segmentation. Together, our work reveals an instance of synchronous clocks timing a patterning process and controlling the development of the vertebral column from the notochord.