Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/117320
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Type: | Journal article |
Title: | Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis |
Author: | Łuksza, M. Kanaan, J. Marthiens, V. Lane, S. Jones, K. Terret, M. Basto, R. Verlhac, M. |
Citation: | The Journal of Cell Biology, 2018; 217(10):3416-3430 |
Publisher: | Rockefeller University Press |
Issue Date: | 2018 |
ISSN: | 0021-9525 1540-8140 |
Statement of Responsibility: | Marion Manil-Ségalen, Małgorzata Łuksza, Joanne Kanaan, Véronique Marthiens, Simon I.R. Lane, Keith T. Jones, Marie-Emilie Terret, Renata Basto, Marie-Hélène Verlhac |
Abstract: | Mouse female meiotic spindles assemble from acentriolar microtubule-organizing centers (aMTOCs) that fragment into discrete foci. These are further sorted and clustered to form spindle poles, thus providing balanced forces for faithful chromosome segregation. To assess the impact of aMTOC biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master microtubule-organizing center regulator. Excessive microtubule nucleation from these fragmented aMTOCs accelerated spindle assembly dynamics. Prematurely formed spindles promoted the breakage of three different fragilized bivalents, generated by the presence of recombined Lox P sites. Reducing the density of microtubules significantly diminished the extent of chromosome breakage. Thus, improper spindle forces can lead to widely described yet unexplained chromosomal structural anomalies with disruptive consequences on the ability of the gamete to transmit an uncorrupted genome. |
Keywords: | Oocytes Chromosomes, Mammalian Microtubule-Organizing Center Animals Mice, Transgenic Mice Meiosis Female Spindle Apparatus Gene Editing |
Rights: | © 2018 Manil-Ségalen et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https:// creativecommons .org/ licenses/ by/ 4 .0/ ). |
DOI: | 10.1083/jcb.201806072 |
Published version: | http://dx.doi.org/10.1083/jcb.201806072 |
Appears in Collections: | Aurora harvest 3 Genetics publications |
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hdl_117320.pdf | Published version | 2.77 MB | Adobe PDF | View/Open |
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