Mitotic waves in frog egg extracts: Transition from phase waves to trigger waves

Abstract

The cell cycle clock network centers on the cyclin-dependent kinase (Cdk1), such that its oscillatory rising and falling activity directs the cell through a series of steps which define one mitotic cycle. When a collection of these oscillators couple, they can synchronize. In particular, early embryogenesis is marked by a series of synchronous and fast cell divisions across the length of the embryo in various systems, e.g. Drosophila (approximately 0.5 mm in length) and Xenopus (approximately 1.2 mm in diameter). However, the large size of these embryos implies a faster coordinating effect than diffusion can control by itself. Two types of waves have been suggested as a mechanism for such spatial coordination: phase waves and trigger waves, which can be distinguished by both the speeds at which they propagate and the biochemical mechanisms behind their formation. Here, by using Xenopus laevis egg extracts and a Cdk1 FRET sensor to study the time dependence of mitotic waves, we show a transition from phase waves to trigger waves for the first time. We show how the addition of nuclei entrains the system more quickly to the trigger wave regime. We also demonstrate that the system is entrained almost immediately when metaphase-arrested extracts initiate the waves from the boundary. Finally, we complement experiments with computational modeling showing how the observed cell cycle period and wave speed depend on transient dynamics and underlying cell cycle oscillator properties. Our work argues that the transition of fast phase waves to slower trigger waves in the spatial coordination of the cell division cycle occurs as a transient effect due to the time required for trigger waves to entrain the system. Moreover, we argue that trigger waves play a role in spatial coordination, and that both phase and trigger waves are a manifestation of a common biological process undergoing these transient dynamics.

Collective effects of cell cleavage dynamics

“…Similarly, crosstalk of trigger and sweep waves has been observed later on in Drosophila and Xenopus extracts, when the cell cycle slows down, potentially upon depletion of resources in the system (Vergassola et al, 2018;Nolet et al, 2020;Puls et al, 2024).…”

The nuclear-cytoplasmic ratio controls the cell cycle period in compartmentalized frog egg extract

“…Most studies have focused on a specific event or cell cycle stage, either interphase or mitosis. In this work, we explore how cell cycle duration is influenced by the nucleus, which has been proposed to enhance the robustness of cell cycle oscillations (27,28) and act as a pacemaker to spatially coordinate the cell cycle via mitotic waves (29)(30)(31). Translocation of Cdk1-cyclinB complexes from the cytoplasm to the nucleus introduces resilience to the process of mitotic entry (32) and influences the period of cell cycle oscillations (28).…”