Nuclei determine the spatial origin of mitotic waves.

Abstract

Traveling waves play an essential role in coordinating mitosis over large distances, but what determines the spatial origin of mitotic waves remains unclear. Here, we show that such waves initiate at pacemakers, regions that oscillate faster than their surroundings. In cell-free extracts of <i>Xenopus laevis</i> eggs, we find that nuclei define such pacemakers by concentrating cell cycle regulators. In computational models of diffusively coupled oscillators that account for nuclear import, nuclear positioning determines the pacemaker location. Furthermore, we find that the spatial dimensions of the oscillatory medium change the nuclear positioning and strongly influence whether a pacemaker is more likely to be at a boundary or an internal region. Finally, we confirm experimentally that increasing the system width increases the proportion of pacemakers at the boundary. Our work provides insight into how nuclei and spatial system dimensions can control local concentrations of regulators and influence the emergent behavior of mitotic waves.