Visualizing the metazoan proliferation-quiescence decision in vivo

  1. Rebecca C Adikes
  2. Abraham Q Kohrman
  3. Michael A Q Martinez
  4. Nicholas J Palmisano
  5. Jayson J Smith
  6. Taylor N Medwig-Kinney
  7. Mingwei Min
  8. Maria Danielle Sallee
  9. Ononnah B Ahmed
  10. Nuri Kim
  11. Simeiyun Liu
  12. Robert D Morabito
  13. Nicholas Weeks
  14. Qinyun Zhao
  15. Wan Zhang
  16. Jessica L Feldman
  17. Michalis Barkoulas
  18. Ariel M Pani
  19. Sabrina Leigh Spencer
  20. Benjamin Louis Martin
  21. David Q Matus  Is a corresponding author
  1. Stony Brook University, United States
  2. University of Colorado-Boulder, United States
  3. Stanford University, United States
  4. Imperial College London, United Kingdom
  5. University of Virginia, United States

Abstract

Cell proliferation and quiescence are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these key events of the cell cycle in C. elegans and zebrafish through live-cell imaging. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from quiescent cells in G0, revealing a possible commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. Finally, we derive a predictive model of future proliferation behavior in C. elegans based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell cycle control in a wide-range of developmental contexts.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Rebecca C Adikes

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Abraham Q Kohrman

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook University, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3726-1090
  3. Michael A Q Martinez

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1178-7139
  4. Nicholas J Palmisano

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jayson J Smith

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Taylor N Medwig-Kinney

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7989-3291
  7. Mingwei Min

    Chemistry and Biochemistry, University of Colorado-Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9050-5330
  8. Maria Danielle Sallee

    Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ononnah B Ahmed

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nuri Kim

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Simeiyun Liu

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Robert D Morabito

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Nicholas Weeks

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Qinyun Zhao

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Wan Zhang

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Jessica L Feldman

    Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5210-5045
  17. Michalis Barkoulas

    Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1974-7668
  18. Ariel M Pani

    University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Sabrina Leigh Spencer

    Biochemistry, University of Colorado-Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5798-3007
  20. Benjamin Louis Martin

    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5474-4492
  21. David Q Matus

    Biochemistry and Cell Biology, Stony Brook University, Stony Brook, United States
    For correspondence
    david.matus@stonybrook.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1570-5025

Funding

National Institutes of Health (1R01GM121597)

  • David Q Matus

National Institutes of Health (DP2GM1191136)

  • Sabrina Leigh Spencer

National Institutes of Health (DP2-CA238330)

  • Jessica L Feldman

American Cancer Society (RSG-18-008-01)

  • Sabrina Leigh Spencer

Pew Charitable Trusts

  • Sabrina Leigh Spencer

Boettcher Foundation

  • Sabrina Leigh Spencer

Searle Scholars Program (SSP-2016-1533)

  • Sabrina Leigh Spencer

National Institutes of Health (1K99GM13548901)

  • Maria Danielle Sallee

National Institutes of Health (1R01GM124282)

  • Benjamin Louis Martin

Damon Runyon Cancer Research Foundation (DRR-47-17)

  • Benjamin Louis Martin
  • David Q Matus

National Science Foundation (IOS 1452928)

  • Benjamin Louis Martin

Pershing Square Sohn Cancer Research Alliance

  • Benjamin Louis Martin

National Institutes of Health (1F32133131)

  • Rebecca C Adikes

National Institutes of Health (F31GM128319)

  • Abraham Q Kohrman

American Cancer Society (132969-PF-18-226-01-CSM)

  • Nicholas J Palmisano

National Institutes of Health (F31HD1000091)

  • Taylor N Medwig-Kinney

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 National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2012-1932 - R2 - 1.15.21- FI) of Stony Brook University. The protocol was approved by the Office of Research Compliance of Stony Brook University.

Reviewing Editor

  1. Margot L K Williams, Baylor College of Medicine, United States

Publication history

  1. Received: September 18, 2020
  2. Accepted: December 21, 2020
  3. Accepted Manuscript published: December 22, 2020 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

Copyright

© 2020, Adikes 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. Rebecca C Adikes
  2. Abraham Q Kohrman
  3. Michael A Q Martinez
  4. Nicholas J Palmisano
  5. Jayson J Smith
  6. Taylor N Medwig-Kinney
  7. Mingwei Min
  8. Maria Danielle Sallee
  9. Ononnah B Ahmed
  10. Nuri Kim
  11. Simeiyun Liu
  12. Robert D Morabito
  13. Nicholas Weeks
  14. Qinyun Zhao
  15. Wan Zhang
  16. Jessica L Feldman
  17. Michalis Barkoulas
  18. Ariel M Pani
  19. Sabrina Leigh Spencer
  20. Benjamin Louis Martin
  21. David Q Matus
(2020)
Visualizing the metazoan proliferation-quiescence decision in vivo
eLife 9:e63265.
https://doi.org/10.7554/eLife.63265
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