Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle

• Published in: Nature (London) Vol. 500; no. 7464; pp. 603 - 607
• Main Authors: Chang, Jeremy B, Ferrell, Jr, James E
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 29.08.2013
• Subjects: Action Potentials; Animals; CDC2 Protein Kinase - metabolism; Cell cycle; Cell Cycle Proteins - antagonists & inhibitors; Cell Extracts; Confidence intervals; Cytoplasm; Cytoplasm - drug effects; Cytoplasm - enzymology; Cytoplasm - metabolism; Diffusion; Eggs; Enzyme Activation; Genetic aspects; Kinases; Microscopy; Mineral oils; Mitosis; Mitosis - drug effects; Movement - drug effects; Ovum - cytology; Ovum - drug effects; Ovum - enzymology; Ovum - metabolism; Partial differential equations; Physiological aspects; Propagation; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - antagonists & inhibitors; Proteins; Pyrimidines - pharmacology; Sperm; Studies; Xenopus; Xenopus laevis; Xenopus Proteins - antagonists & inhibitors; Zygote - cytology; Zygote - drug effects; Zygote - enzymology; Zygote - metabolism; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12321

Despite the large size of the Xenopus laevis egg (approximately 1.2 mm diameter), a fertilized egg rapidly proceeds through mitosis in a spatially coordinated fashion. Mitosis is initiated by a bistable system of regulatory proteins centred on Cdk1 (refs 1, 2), raising the possibility that this spatial coordination could be achieved through trigger waves of Cdk1 activity. Using an extract system that performs cell cycles in vitro, here we show that mitosis does spread through Xenopus cytoplasm via trigger waves, propagating at a linear speed of approximately 60 µm min(-1). Perturbing the feedback loops that give rise to the bistability of Cdk1 changes the speed and dynamics of the waves. Time-lapse imaging of intact eggs argues that trigger waves of Cdk1 activation are responsible for surface contraction waves, ripples in the cell cortex that precede cytokinesis. These findings indicate that Cdk1 trigger waves help ensure the spatiotemporal coordination of mitosis in large eggs. Trigger waves may be an important general mechanism for coordinating biochemical events over large distances.