Abstract
AbstractThe 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) andXenopus(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 usingXenopus laevisegg 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.
Publisher
Cold Spring Harbor Laboratory
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