Towards a Quantitative Understanding of Spontaneous Mitotic Waves

Various models have been developed to capture the mechanism of the mitotic clock. Taken together, they describe how the cyclinB-Cdk1 complex directs the cell through a series of steps which define one mitotic cycle. This regulation facilitates the longevity of multicellular organisms by enforcing a regular, clock-like timing of mitotic events. When a collection of these oscillators couple, they synchronize. In particular, in various systems—e.g. Drosophila and Xenopus—early embryogenesis is marked by a series of synchronous cell divisions across the embryo, exceding the scope of a diffusive signal. Instead, we explore a known spatial coordination mechanism: waves. Using Xenopus extracts and a Cdk1-FRET sensor, we exploit a novel approach utilizing metaphase-arrested extracts to produce one-dimensional directed mitotic waves. We probe the possible differences between waves in systems with or without reconstituted nuclei. We find the speed of the former to be significantly slower, suggesting an active role for nuclei in wave propogation. Moreover, we quantify the wave speed  over time, showing a clear relationship between speed and the time Cdk1 spends in the active state. In total, we display a unique method for directly visualzing and characterizing biochemical mitotic waves.