MPS1 promotes timely spindle bipolarization to prevent kinetochore-microtubule attachment errors in oocytes.

Abstract

Incorrect kinetochore-microtubule attachment leads to chromosome segregation errors. The risk of incorrect attachment is high in acentrosomal oocytes, where kinetochores are surrounded by randomly oriented microtubules until spindle bipolarization. Regulation of the temporal relationship between acentrosomal spindle bipolarization and kinetochore-microtubule attachment is unknown. Here, we show that in mouse oocytes, MPS1, a kinase more active at kinetochores with less stable microtubule attachment, promotes timely spindle bipolarization before kinetochores stably attach to microtubules. In MPS1-inhibited oocytes, spindle bipolarization is delayed and depends on microtubules stably attached to kinetochores, resulting in incorrect attachments. We propose a two-step kinetochore-based model where unstable and stable attachment states act sequentially for acentrosomal spindle assembly to reduce the risk of egg aneuploidy.