Periodic inhibition of Erk activity drives sequential somite segmentation

Sequential segmentation creates modular body plans of diverse metazoan embryos 1 – 4 . Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation 4 . 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 neighbouring cells to discretely establish somite boundaries in zebrafish 5 . Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species 3 , 4 , 6 – 8 . Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients. The zebrafish segmentation clock drives sequential segmentation of somites by periodically lowering double-phosphorylated Erk and therefore projecting its oscillation on the double-phosphorylated Erk gradient.