Periodic inhibition of Erk activity drives sequential somite segmentation

M. Fethullah Simsek (), Angad Singh Chandel, Didar Saparov, Oriana Q. H. Zinani, Nicholas Clason and Ertuğrul M. Özbudak ()
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M. Fethullah Simsek: Cincinnati Children’s Hospital Medical Center
Angad Singh Chandel: Cincinnati Children’s Hospital Medical Center
Didar Saparov: Cincinnati Children’s Hospital Medical Center
Oriana Q. H. Zinani: Cincinnati Children’s Hospital Medical Center
Nicholas Clason: University of Cincinnati
Ertuğrul M. Özbudak: Cincinnati Children’s Hospital Medical Center

Nature, 2023, vol. 613, issue 7942, 153-159

Abstract: Abstract Sequential segmentation creates modular body plans of diverse metazoan embryos1–4. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation4. 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 zebrafish5. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species3,4,6–8. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.

Date: 2023
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DOI: 10.1038/s41586-022-05527-x

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