Microtubule Dynamics Scale with Cell Size to Set Spindle Length and Assembly Timing

Successive cell divisions during embryonic cleavage create increasingly smaller cells, so intracellular structures must adapt accordingly. Mitotic spindle size correlates with cell size, but the mechanisms for this scaling remain unclear. Using live cell imaging, we analyzed spindle scaling during e...

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Bibliographic Details
Published in:Developmental cell Vol. 45; no. 4; pp. 496 - 511.e6
Main Authors: Lacroix, Benjamin, Letort, Gaëlle, Pitayu, Laras, Sallé, Jérémy, Stefanutti, Marine, Maton, Gilliane, Ladouceur, Anne-Marie, Canman, Julie C., Maddox, Paul S., Maddox, Amy S., Minc, Nicolas, Nédélec, François, Dumont, Julien
Format: Journal Article
Language:English
Published: United States Elsevier Inc 21-05-2018
Elsevier
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Summary:Successive cell divisions during embryonic cleavage create increasingly smaller cells, so intracellular structures must adapt accordingly. Mitotic spindle size correlates with cell size, but the mechanisms for this scaling remain unclear. Using live cell imaging, we analyzed spindle scaling during embryo cleavage in the nematode Caenorhabditis elegans and sea urchin Paracentrotus lividus. We reveal a common scaling mechanism, where the growth rate of spindle microtubules scales with cell volume, which explains spindle shortening. Spindle assembly timing is, however, constant throughout successive divisions. Analyses in silico suggest that controlling the microtubule growth rate is sufficient to scale spindle length and maintain a constant assembly timing. We tested our in silico predictions to demonstrate that modulating cell volume or microtubule growth rate in vivo induces a proportional spindle size change. Our results suggest that scalability of the microtubule growth rate when cell size varies adapts spindle length to cell volume. [Display omitted] •Microtubule dynamics scales with cell size during embryonic development•Microtubule growth rate controls spindle length adaptation to cell size•Timing of spindle assembly is constant and independent of spindle and cell size•Microtubule growth rate regulates spindle length and assembly timing During early embryonic development, the mitotic spindle scales with decreasing cell size across successive reductive divisions. Lacroix et al. uncover, using in vivo and in silico analyses, a common scaling mechanism whereby spindle microtubule growth rate is coupled to cell volume for size scaling while maintaining constant spindle assembly timing.
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AUTHOR CONTRIBUTIONS
B.L. and J.D. conceived the project with input from all authors. B.L. performed all of the experiments, except those specifically attributed to other authors. L.P. performed the CLβL experiments and analysis. J.S. performed the sea urchin microinjection experiments with input from N.M. G.M. performed the C. elegans microinjection experiments. M.S. and J.C.C. generated some strains used in this study. A.M.L. performed some image analyses. B.L., J.D., G.L. and F.N. conceived the in silico model, and G.L. and F.N. extended Cytosim to implement it. G.L. performed the computer simulations under F.N. supervision. B.L. and J.D. made the figures and wrote the manuscript with input from all authors.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2018.04.022