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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....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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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. |
format | Online Article Text |
id | pubmed-6589792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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