Spatial heterogeneity accelerates phase-to-trigger wave transitions in frog egg extracts.

Cyclin-dependent kinase 1 (Cdk1) activity rises and falls throughout the cell cycle: a cell-autonomous process called mitotic oscillations. Mitotic oscillators can synchronize when spatially coupled, facilitating rapid, synchronous divisions in large early embryos of Drosophila (0.5 mm) and Xenopus (1.2 mm). Diffusion alone cannot achieve such long-range coordination. Instead, studies proposed mitotic waves-phase and trigger waves-as mechanisms of the coordination. How waves establish over time remains unclear. Using Xenopus laevis egg extracts and a Cdk1 Förster resonance energy transfer sensor, we observe a transition from phase to trigger wave dynamics in initially homogeneous cytosol. Spatial heterogeneity promotes this transition. Adding nuclei accelerates entrainment. The system transitions almost immediately when driven by metaphase-arrested extracts. Numerical simulations suggest phase waves appear transiently as trigger waves take time to entrain the system. Therefore, we show that both waves belong to a single biological process capable of coordinating the cell cycle over long distances.