Restaging the Spindle Assembly Checkpoint in Female Mammalian Meiosis I

Abstract

In mammalian somatic cells, the spindle assembly checkpoint (SAC) is indispensable forensuring the fidelity of chromosome segregation by delaying cell-cycle progression in theface of even a single misaligned chromosome. In contrast, the role of the SAC inunperturbed mammalian oocytes is less well defined as progression through meiosis I isunaltered in mouse oocytes in the presence of one or a few misaligned chromosomes.Furthermore, attempts to disable the function of the SAC protein, Mad2, in mouseoocytes have produced conflicting results. To gain further insight into SAC functionduring female mammalian meiosis I, we recently utilised a morpholino-based antisenseapproach to deplete the majority of Mad2 in mouse oocytes. Our results define a clearrole for Mad2 in ensuring the proper timing of meiosis I events and ultimately, inensuring the fidelity of homologue disjunction. We discuss the implications of theseresults for the regulation of meiosis I in mammalian oocytes and for the genesis of humananeuploidy.