Tissue-wide Erk oscillations set the pace of zebrafish notochord segmentation

The generation of a segmented body plan is a hallmark of vertebrate development. Biological oscillators provide a mechanism for timing the formation of repeated structures, yet to date only a few examples of signaling oscillators have been identified in development. Here, we show that the periodic addition of mineralizing segments in the zebrafish notochord is timed by tissue-wide oscillations of Erk activity. We report delayed oscillations in the transcription of spry and dusp genes, suggesting that they act as negative feedback. Erk activity is regulated by EGFR signaling and increased egf expression marks the emergence of oscillations via an infinite-period bifurcation, revealing the mechanism controlling the onset of notochord segmentation and the tunability of the oscillator. Our results show a remarkable degree of synchronization across the notochord and reveal an instance of biological clocks timing a patterning process, crucial for the development of the vertebral column from the notochord.