Kinetochores promote timely spindle bipolarization to prevent microtubule attachment errors in oocytes

Abstract

SummaryIncorrect kinetochore-microtubule attachment leads to chromosome segregation errors. The risk of incorrect attachments is particularly high in acentrosomal oocytes, where kinetochores are surrounded by randomly oriented microtubules until spindle bipolarization. How the timing of acentrosomal spindle bipolarization is coordinated with kinetochore-microtubule attachment is unknown. Here, we show that in mouse oocytes, kinetochores promote spindle bipolarization when microtubule attachment is unstable in early prometaphase. The kinetochore kinase MPS1 allows this function by regulating multiple pathways, including those mediated by the kinetochore proteins NDC80-NUF2 at their C-terminal domains and the antiparallel microtubule crosslinker PRC1. Inhibition of MPS1 delays spindle bipolarization to late prometaphase, thereby increasing incorrect kinetochore-microtubule attachments. Artificially accelerating spindle bipolarization by overexpressing KIFC1 prevents incorrect kinetochore-microtubule attachment in MPS1-inhibited oocytes. Thus, kinetochores autonomously promote timely acentrosomal spindle bipolarization prior to stabilizing microtubule attachment, thereby reducing the risk of egg aneuploidy.