Elsevier

Developmental Biology

Volume 470, February 2021, Pages 147-153
Developmental Biology

Temperature-Induced uncoupling of cell cycle regulators

https://doi.org/10.1016/j.ydbio.2020.11.010Get rights and content
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Highlights

  • Cell cycle processes are conserved in early Drosophila embryos across a wide temperature range.

  • The duration of individual cell cycle steps is consistent with an Arrhenius model.

  • Prophase is the process most sensitive to temperature and likely controlled by a different regulatory mechanism.

  • Pharmacological approaches and FRET sensor show that Cdk1 drives entry into prometaphase, but not prophase.

The early stages of development involve complex sequences of morphological changes that are both reproducible from embryo to embryo and often robust to environmental variability. To investigate the relationship between reproducibility and robustness we examined cell cycle progression in early Drosophila embryos at different temperatures. Our experiments show that while the subdivision of cell cycle steps is conserved across a wide range of temperatures (5–35 ​°C), the relative duration of individual steps varies with temperature. We find that the transition into prometaphase is delayed at lower temperatures relative to other cell cycle events, arguing that it has a different mechanism of regulation. Using an in vivo biosensor, we quantified the ratio of activities of the major mitotic kinase, Cdk1 and one of the major mitotic phosphatases PP1. Comparing activation profile with cell cycle transition times at different temperatures indicates that in early fly embryos activation of Cdk1 drives entry into prometaphase but is not required for earlier cell cycle events. In fact, chromosome condensation can still occur when Cdk1 activity is inhibited pharmacologically. These results demonstrate that different kinases are rate-limiting for different steps of mitosis, arguing that robust inter-regulation may be needed for rapid and ordered mitosis.

Keywords

Regulation of biological networks
Cell cycle regulation
Arrhenius dependence

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Current affiliation: HHMI Life Sciences Associate, Departments of Neuroscience and of Cell Biology, Kavli Institute for Neuroscience, Yale University School of Medicine.