Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
- Harvard Medical School, United States
- The Hospital for Sick Children, Canada
Abstract
Cell size uniformity in healthy tissues suggests that control mechanisms might coordinate cell growth and division. We derived a method to assay whether cellular growth rates depend on cell size, by monitoring how variance in size changes as cells grow. Our data revealed that, twice during the cell cycle, growth rates are selectively increased in small cells and reduced in large cells, ensuring cell size uniformity. This regulation was also observed directly by monitoring nuclear growth in live cells. We also detected cell-size-dependent adjustments of G1 length, which further reduce variability. Combining our assays with chemical/genetic perturbations confirmed that cells employ two strategies, adjusting both cell cycle length and growth rate, to maintain the appropriate size. Additionally, although Rb signaling is not required for these regulatory behaviors, perturbing Cdk4 activity still influences cell size, suggesting that the Cdk4 pathway may play a role in designating the cell's target size.
Data availability
All data presented in this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (FRN-343437)
- Ran Kafri
National Institutes of Health (R01GM026875)
- Marc W Kirschner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bruce Edgar, University of Utah, United States
Version history
- Received: March 18, 2017
- Accepted: June 7, 2018
- Accepted Manuscript published: June 11, 2018 (version 1)
- Version of Record published: July 4, 2018 (version 2)
Copyright
© 2018, Ginzberg 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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Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity
eLife 7:e26957.
https://doi.org/10.7554/eLife.26957
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