Actin promotes chromosome aggregation and accurate chromosome segregation in mammalian oocytes

Abstract

Accurate chromosome segregation during meiosis is essential for the formation of a new life. During meiosis, spindle microtubules bind to the chromosomes’ kinetochores and arms in order to separate the genetic material. Chromosome movements during cell division are thus generally thought to be driven by microtubules. Whether actin moves chromosomes in mammalian mitosis or meiosis is unknown. In this thesis, I studied the prolonged gap phase between nuclear envelope breakdown and the onset of spindle microtubule assembly in human and porcine oocytes. Strikingly, I found that actin moves chromosomes during this early phase of meiosis. In particular, actin transiently clusters the oocytes’ chromosomes into an aggregate. Chromosome aggregation is driven by Formin-2- and Spire-nucleated actin cables. The actin cables associate with the chromosomes’ kinetochores and push on chromosome arms while contracting, and thereby drive chromosome aggregation. I show that chromosome aggregation prevents chromosome losses during the prolonged gap phase between nuclear envelope breakdown and the onset of spindle microtubule assembly. In addition, chromosome aggregation limits the formation of premature incorrect kinetochore-microtubule attachments. Moreover, I present data that reveal additional unexpected roles for actin and myosins in later stages of meiosis. Together, my data establish essential roles for actin-dependent chromosome movements in preventing aneuploidy in mammalian oocytes.