Nuclei determine the spatial origin of mitotic waves

  1. Felix Eduard Nolet
  2. Alexandra Vandervelde
  3. Arno Vanderbeke
  4. Liliana Pineros
  5. Jeremy B Chang
  6. Lendert Gelens  Is a corresponding author
  1. KU Leuven, Belgium
  2. University of California San Francisco, United States

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 which oscillate faster than their surroundings. In cell-free extracts of Xenopus laevis 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, influencing the emergent behavior of mitotic waves.

Data availability

All the data generated during the study are summarized and provided in the manuscript and supporting files. Source files have been provided for Figure 1, Figure 1-Figure Supplement 3, Figure 2, Figure 5-Figure Supplement 1, Box 2, Video 1 and Video 2 in the format of microscopy videos. Additionally, representative microscopy videos of all different conditions are provided as a Zenodo dataset (http://doi.org/10.5281/zenodo.3736728). The numerical codes that were used, together with an overview table of the performed experiments, are available through GitHub (Nolet, 2020).

Article and author information

Author details

  1. Felix Eduard Nolet

    Laboratory of Dynamics in Biological Systems, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9300-6302
  2. Alexandra Vandervelde

    Laboratory of Dynamics in Biological Systems, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  3. Arno Vanderbeke

    Laboratory of Dynamics in Biological Systems, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7240-8377
  4. Liliana Pineros

    Laboratory of Dynamics in Biological Systems, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeremy B Chang

    Department of Biosystems, University of California San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lendert Gelens

    Laboratory of Dynamics in Biological Systems, KU Leuven, Leuven, Belgium
    For correspondence
    lendert.gelens@kuleuven.be
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7290-9561

Funding

Research Foundation - Flanders (GOA5317N)

  • Lendert Gelens

KU Leuven Research Fund (C14/18/084)

  • Lendert Gelens

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the KU Leuven. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the KU Leuven. The protocol was approved by the Committee on the Ethics of Animal Experiments of the KU Leuven (ECD permit Number: P165/2016
).

Reviewing Editor

  1. Stefano Di Talia, Duke University, United States

Publication history

  1. Received: October 18, 2019
  2. Accepted: May 22, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Version of Record published: June 24, 2020 (version 2)

Copyright

© 2020, Nolet et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Felix Eduard Nolet
  2. Alexandra Vandervelde
  3. Arno Vanderbeke
  4. Liliana Pineros
  5. Jeremy B Chang
  6. Lendert Gelens
(2020)
Nuclei determine the spatial origin of mitotic waves
eLife 9:e52868.
https://doi.org/10.7554/eLife.52868
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