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 Caenorhabditis 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.
Highlights
Organismal development requires a delicate balance between cell proliferation and cell cycle exit
When cyclin-dependent kinase (CDK) activity increases during cell-cycle entry, the nuclear localization signal (NLS) is masked and DNA helicase B (DHB) re-localizes to the cytoplasm (Figure 1B)
We co-expressed his-58/histone H2B fused to 2xmKate2 or green fluorescent protein (GFP), respectively, which is separated from DHB by a P2A self-cleaving viral peptide (Ahier and Jarriault, 2014)
Summary
Organismal development requires a delicate balance between cell proliferation and cell cycle exit. After several rounds of embryonic cell division, the gap phases are introduced, coincident in many organisms with cell fate decisions and the execution of morphogenetic cell behaviors (Foe, 1989; Grosshans and Wieschaus, 2000). These gap phases are believed to function as commitment points for cell-cycle progression decisions.
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