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.
- Ran Kafri
- Marc W Kirschner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Bruce Edgar, Reviewing Editor, University of Utah, United States
- Received: March 18, 2017
- Accepted: June 7, 2018
- Accepted Manuscript published: June 11, 2018 (version 1)
© 2018, Ginzberg et al.
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