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

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....

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Autores principales: Letort, Gaelle, Bennabi, Isma, Dmitrieff, Serge, Nedelec, François, Verlhac, Marie-Hélène, Terret, Marie-Emilie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589792/
https://www.ncbi.nlm.nih.gov/pubmed/30650011
http://dx.doi.org/10.1091/mbc.E18-10-0644
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author Letort, Gaelle
Bennabi, Isma
Dmitrieff, Serge
Nedelec, François
Verlhac, Marie-Hélène
Terret, Marie-Emilie
author_facet Letort, Gaelle
Bennabi, Isma
Dmitrieff, Serge
Nedelec, François
Verlhac, Marie-Hélène
Terret, Marie-Emilie
author_sort Letort, Gaelle
collection PubMed
description 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.
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spelling pubmed-65897922019-07-02 A computational model of the early stages of acentriolar meiotic spindle assembly Letort, Gaelle Bennabi, Isma Dmitrieff, Serge Nedelec, François Verlhac, Marie-Hélène Terret, Marie-Emilie Mol Biol Cell Articles 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. The American Society for Cell Biology 2019-03-21 /pmc/articles/PMC6589792/ /pubmed/30650011 http://dx.doi.org/10.1091/mbc.E18-10-0644 Text en © 2019 Letort et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Letort, Gaelle
Bennabi, Isma
Dmitrieff, Serge
Nedelec, François
Verlhac, Marie-Hélène
Terret, Marie-Emilie
A computational model of the early stages of acentriolar meiotic spindle assembly
title A computational model of the early stages of acentriolar meiotic spindle assembly
title_full A computational model of the early stages of acentriolar meiotic spindle assembly
title_fullStr A computational model of the early stages of acentriolar meiotic spindle assembly
title_full_unstemmed A computational model of the early stages of acentriolar meiotic spindle assembly
title_short A computational model of the early stages of acentriolar meiotic spindle assembly
title_sort computational model of the early stages of acentriolar meiotic spindle assembly
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589792/
https://www.ncbi.nlm.nih.gov/pubmed/30650011
http://dx.doi.org/10.1091/mbc.E18-10-0644
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