Abstract: Sequential segmentation creates modular body plans of diverse metazoan embryos. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation. However, how cells are primed to form a segment boundary at a specific location remains unclear. Here we developed precise reporters for the clock and double phosphorylated ERK (ppERK) gradient in zebrafish. We show that the Her1–Her7 oscillator drives segmental commitment by periodically lowering ppERK, therefore projecting its oscillation onto the ppERK gradient. Pulsatile inhibition of the ppERK gradient can fully substitute for the role of the clock, and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of ppERK, which in turn enables neighboring cells to discretely establish somite boundaries in zebrafish. We here propose a “Clock-dependent Oscillatory Gradient (COG)” model in which the clock periodically triggers discrete shifts of the positional information. The COG model explains all experimental observations and effectively replaces the long-standing clock and wavefront model in the field. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.
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