An actin-dependent spindle position checkpoint ensures the asymmetric division in mouse oocytes.

Aïcha Metchat,Julius M Hossain,Jan Ellenberg,Antonio Z Politi,Manuel Eguren,Sébastien Huet

doi:10.1038/ncomms8784

Aïcha Metchat, Julius M Hossain + Show 4 more

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https://doi.org/10.1038/ncomms8784

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Journal: Nature communications	Publication Date: Jul 15, 2015
Citations: 8	License type: CC BY 4.0

Affiliation: European Molecular Biology Laboratory

Abstract

Faithful chromosome segregation, during meiosis, is of critical importance to prevent aneuploidy in the resulting embryo. In mammalian oocytes, the segregation of homologous chromosomes takes place with the spindle located at the cell's periphery. The spindle is often assembled close to the centre of the cell, which necessitates the actin network for spindle transport to the cell cortex. In this study, we investigate how the segregation of chromosomes is coordinated with the positioning of the metaphase I spindle. We develop different assays to perturb the spindle's position and to delay its relocation to the cell periphery. We find that anaphase is delayed until the spindle is positioned in close proximity with the oocyte cortex. We further show that the metaphase arrest is dependent on a functional actin network, in addition to the spindle assembly checkpoint. Our work provides the first evidence for the existence of a functional spindle position checkpoint.

Highlights

Faithful chromosome segregation, during meiosis, is of critical importance to prevent aneuploidy in the resulting embryo
We demonstrate the existence of a mechanism similar to the so-called ‘spindle position checkpoint’ (SPC) in yeast[24], which prevents chromosome segregation until the spindle is positioned in the cortical position
To quantitatively determine how the spindle is relocated from the centre to the cortex for chromosome segregation, we performed fourdimensional live-cell imaging of oocytes, in which microtubules were labelled with MAP4-GFP1,25, from the metaphase to anaphase stages using confocal microscope imaging

Summary

Introduction

Faithful chromosome segregation, during meiosis, is of critical importance to prevent aneuploidy in the resulting embryo. During meiosis I, all chromosomes usually achieve a stable biorientation 2–3 h before the onset of anaphase[1,4] During this delay, a dynamic actin network spanning throughout the large cytoplasm moves the spindle from the centre toward the cortex of the oocyte[18,19,20,21,22,23]. The spindle checkpoint protein Mad[2] remains evident at kinetochores in late metaphase I, despite the fact that correct attachment of kinetochore fibres to the chromosome is achieved before spindle relocation[1,4] These events suggest that chromosome biorientation may not be the sole mechanism that is monitored to prevent precocious chromosome segregation in oocytes. We demonstrate the existence of a mechanism similar to the so-called ‘spindle position checkpoint’ (SPC) in yeast[24], which prevents chromosome segregation until the spindle is positioned in the cortical position

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Conclusion