Visualizing the metazoan proliferation-quiescence decision in vivo
- Stony Brook University, United States
- University of Colorado-Boulder, United States
- Stanford University, United States
- Imperial College London, United Kingdom
- 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
Michael A Q Martinez
Taylor N Medwig-Kinney
Michalis Barkoulas
Sabrina Leigh Spencer
Benjamin Louis Martin
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.
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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Visualizing the metazoan proliferation-quiescence decision in vivo
eLife 9:e63265.
https://doi.org/10.7554/eLife.63265
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