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A computational model of the early stages of acentriolar meiotic spindle assembly.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Letort, Gaelle 
Bennabi, Isma 
Dmitrieff, Serge 
Nedelec, François 
Verlhac, Marie-Hélène 

Abstract

The mitotic spindle is an ensemble of microtubules responsible for the repartition of the chromosomal content between the two daughter cells during division. In metazoans, spindle assembly is a gradual process involving dynamic microtubules and recruitment of numerous associated proteins and motors. During mitosis, centrosomes organize and nucleate the majority of spindle microtubules. In contrast, oocytes lack canonical centrosomes but are still able to form bipolar spindles, starting from an initial ball that self-organizes in several hours. Interfering with early steps of meiotic spindle assembly can lead to erroneous chromosome segregation. Although not fully elucidated, this process is known to rely on antagonistic activities of plus end- and minus end-directed motors. We developed a model of early meiotic spindle assembly in mouse oocytes, including key factors such as microtubule dynamics and chromosome movement. We explored how the balance between plus end- and minus end-directed motors, as well as the influence of microtubule nucleation, impacts spindle morphology. In a refined model, we added spatial regulation of microtubule stability and minus-end clustering. We could reproduce the features of early stages of spindle assembly from 12 different experimental perturbations and predict eight additional perturbations. With its ability to characterize and predict chromosome individualization, this model can help deepen our understanding of spindle assembly.

Description

Keywords

Animals, Cell Nucleus Division, Centrosome, Chromosome Segregation, Chromosomes, Computational Biology, Computer Simulation, Female, Mice, Microtubule-Associated Proteins, Microtubules, Mitosis, Models, Biological, Oocytes, Spindle Apparatus

Journal Title

Mol Biol Cell

Conference Name

Journal ISSN

1059-1524
1939-4586

Volume Title

30

Publisher

American Society for Cell Biology (ASCB)