THE METAPHASE-II ARREST IN MOUSE OOCYTES IS CONTROLLED THROUGH MICROTUBULE-DEPENDENT DESTRUCTION OF CYCLIN-B IN THE PRESENCE OF CSF

In unfertilized eggs from vertebrates, the cell cycle is arrested in m etaphase of the second meiotic division (metaphase II) until fertiliza tion or activation. Maintenance of the long-term meiotic metaphase arr est requires mechanisms preventing the destruction of the maturation p romoting factor (MPF) and the migration of the chromosomes. In frog oo cytes, arrest in metaphase II (M II) is achieved by cytostatic factor (CSF) that stabilizes MPF, a heterodimer formed of cdc2 kinase and cyc lin. At the metaphase/anaphase transition, a rapid proteolysis of cycl in is associated with MPF inactivation. In Drosophila, oocytes are arr ested in metaphase I (M I); however, only mechanical forces generated by the chiasmata seem to prevent chromosome separation. Thus, entirely different mechanisms may be involved in the meiotic arrests in variou s species. We report here that in mouse oocytes a CSF-like activity is involved in the M II arrest (as observed in hybrids composed of fragm ents of metaphase II-arrested oocytes and activated mitotic mouse oocy tes) and that the high activity of MPF is maintained through a continu ous equilibrium between cyclin B synthesis and degradation. In additio n, the presence of an intact metaphase spindle is required for cyclin B degradation. Finally, MPF activity is preferentially associated with the spindle after bisection of the oocyte. Taken together, these obse rvations suggest that the mechanism maintaining the metaphase arrest i n mouse oocytes involves an equilibrium between cyclin synthesis and d egradation, probably controlled by CSF, and which is also dependent up on the three-dimensional organization of the spindle.