Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles

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Abstract

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting.

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Franziska Decker

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Competing interests
The authors declare that no competing interests exist.
David Oriola

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Competing interests
The authors declare that no competing interests exist.
Benjamin Dalton

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Competing interests
The authors declare that no competing interests exist.
Jan Brugues

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

For correspondence
brugues@mpi-cbg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6731-4130

Funding

Human Frontier Science Program (CDA00074/2014)

Jan Brugues

European Molecular Biology Organization (ALTF 483-2016)

David Oriola

Deutsche Forschungsgemeinschaft

Franziska Decker

Max-Planck-Gesellschaft (Open-access funding)

Franziska Decker
David Oriola
Benjamin Dalton
Jan Brugues

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animals were handled according to the directive 2010/63/EU on the protection of animals used for scientific purposes, and the german animal welfare law under the license document number DD24-5131/367/9 from the Landesdirektion Sachsen (Dresden) - Section 24D.

Copyright

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.