Spindle tubulin and MTOC asymmetries may explain meiotic drive in oocytes

Tianyu Wu,Keith T Jones,Simon I R Lane,Stephanie L Morgan

doi:10.1038/s41467-018-05338-7

Abstract

In the first meiotic division (MI) of oocytes, the cortically positioned spindle causes bivalent segregation in which only the centre-facing homologue pairs are retained. ‘Selfish’ chromosomes are known to exist, which bias their spindle orientation and hence retention in the egg, a process known as ‘meiotic drive’. Here we report on this phenomenon in oocytes from F1 hybrid mice, where parental strain differences in centromere size allows distinction of the two homologue pairs of a bivalent. Bivalents with centromere and kinetochore asymmetry show meiotic drive by rotating during prometaphase, in a process dependent on aurora kinase activity. Cortically positioned homologue pairs appear to be under greater stretch than their centre-facing partners. Additionally the cortex spindle-half contain a greater density of tubulin and microtubule organising centres. A model is presented in which meiotic drive is explained by the impact of microtubule force asymmetry on chromosomes with different sized centromeres and kinetochores.

Highlights

In the first meiotic division (MI) of oocytes, the cortically positioned spindle causes bivalent segregation in which only the centre-facing homologue pairs are retained
For all but two bivalents in each oocyte there existed a low level of major satellite asymmetry between the two homologue pairs of a bivalent
Since the analysis of the driving bivalent in F1 mice indicated that the orientation bias was exerted between 2 and 6 h after nuclear envelope breakdown (NEBD), we looked for differences in the cortical and central halves of the spindle that existed during this time window

Summary

Introduction

In the first meiotic division (MI) of oocytes, the cortically positioned spindle causes bivalent segregation in which only the centre-facing homologue pairs are retained. For all but two bivalents in each oocyte there existed a low level of major satellite asymmetry between the two homologue pairs of a bivalent (ratio 0.80, 95% CI: 0.74–0.86; Supplementary Fig. 1a). The homologue pair of the bivalent with the larger major satellite had consistently the smaller minor satellite and the larger kinetochore Spc[24] signal (Fig. 1c; Supplementary Fig. 1b–d).

Results

Conclusion