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

Nature volume 500, pages 603–607 (2013)Cite this article

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Abstract

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 activity3. 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 cytokinesis4,5. 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.

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Figure 1: Trigger waves in Cdk1 activation.
Figure 2: Rapid, linear propagation of mitotic entry and exit through Xenopus cytoplasm.
Figure 3: The Wee1/Myt1 inhibitor PD0166285 accelerates the trigger waves.
Figure 4: Surface contraction waves in intact Xenopus eggs.

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Acknowledgements

We thank H. Funabiki and M. Dasso for providing GFP–NLS protein and constructs, E. Sontag and L. Wang for discussions and calculations, T. Tsai for sharing his unpublished data on the effects of PD0166285 on Xenopus embryos, Q. Yang for helping to build the ordinary differential equation model upon which our partial differential equation model is based, G. Dey, H. Stone and B. Sullivan for discussions, S. Quake and the Quake laboratory for advice, J. Chen and the Chen laboratory for the use of their microscope and discussions, J. Pomerening for discussions and technical advice, the Stanford Cell Sciences Imaging Facility for technical assistance, and members of the Ferrell laboratory for discussions. This work was supported by grants from the National Institutes of Health (GM046383 and GM077544) and by a National Science Foundation Graduate Research Fellowship and a Lieberman Fellowship (to J.B.C.).

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Authors and Affiliations

  1. Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, 94305-5174, California, USA

    Jeremy B. Chang & James E. Ferrell Jr

  2. Department of Biochemistry, Stanford University School of Medicine, Stanford, 94305-5307, California, USA

    James E. Ferrell Jr

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  1. Jeremy B. Chang
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J.B.C. performed experiments and calculations, analysed data and helped write the paper. J.E.F. performed calculations, analysed data and helped write the paper.

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Correspondence to Jeremy B. Chang or James E. Ferrell Jr.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text and Data, Supplementary Figures 1-4 and additional references. (PDF 1030 kb)

Mitotic waves in Xenopus extracts in Teflon tubes

Nuclei appear as green circles that disappear (nuclear envelope breakdown) and reappear (nuclear envelope formation). The channel width is 100 µm. This movie corresponds to the experiment plotted in Fig. 2b. Images were obtained at a rate of 1 image per min and are shown at a rate of 15 frames per sec. (MOV 6009 kb)

Trigger waves vs. phase waves

This video is from the experiment shown in Fig. 2c. Again, the channel width is 100 µm and images were obtained at a rate of 1 image per min and are shown at a rate of 15 frames per sec. (MOV 9244 kb)

Surface contraction waves in fertilized Xenopus eggs

Two waves of pigmentation can be seen just prior to the first mitotic cleavage. Related to Fig. 4d. Images were obtained at a rate of 1 image per 10 sec and are shown at a rate of 75 frames per sec. (MOV 3740 kb)

Surface contraction waves in parthenogenetically-activated Xenopus eggs

Three pairs of waves are seen in this video. Related to Fig. 4e. Images were obtained at a rate of 1 image per 10 sec and are shown at a rate of 75 frames per sec. (MOV 3588 kb)

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Chang, J., Ferrell Jr, J. Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle. Nature 500, 603–607 (2013). https://doi.org/10.1038/nature12321

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