Kinetochore Fibers Are Not Involved in the Formation of the First Meiotic Spindle in Mouse Oocytes, but Control the Exit from the First Meiotic M Phase

Abstract

During meiosis, two successive divisions occur without any intermediate S phase to produce haploid gametes. The first meiotic division is unique in that homologous chromosomes are segregated while the cohesion between sister chromatids is maintained, resulting in a reductional division. Moreover, the duration of the first meiotic M phase is usually prolonged when compared with mitotic M phases lasting 8 h in mouse oocytes.We investigated the spindle assembly pathway and its role in the progression of the first meiotic M phase in mouse oocytes. During the first 4 h, a bipolar spindle forms and the chromosomes congress near the equatorial plane of the spindle without stable kinetochore– microtubule end interactions. This late prometaphase spindle is then maintained for 4 h with chromosomes oscillating in the central region of the spindle. The kinetochore–microtubule end interactions are set up at the end of the first meiotic M phase (8 h after entry into M phase). This event allows the final alignment of the chromosomes and exit from metaphase. The continuous presence of the prometaphase spindle is not required for progression of the first meiotic M phase. Finally, the ability of kinetochores to interact with microtubules is acquired at the end of the first meiotic M phase and determines the timing of polar body extrusion.

Inherent Instability of Correct Kinetochore-Microtubule Attachments during Meiosis I in Oocytes

“…The exact timing of stable correct KT-MT attachment in oocytes, however, remains uncertain. In the 1990s, an electron microscopic study detected stable endon KT-MT attachments at only the very late stage of phase 4 (Brunet et al, 1999). Recent immunostaining studies, however, have revealed end-on KT-MT attachments near phase 3 (Gui and Homer, 2012;Kitajima et al, 2011;Lane et al, 2012), although it is unknown whether these attachments are associated with bivalent stretching.…”

The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint

“…One possibility that would attempt to unify the data is that there are certain types of kinetochore-microtubule attachments that are poorly detected and corrected in oocytes. In addition, end-on microtubule-kinetochore attachments are not formed until very late in meiosis I (Brunet et al 1999). Hence, there is an interest in this study and also in previous studies, in determining whether Auroras have any SAC role in the unusual first division of oocytes.…”

“…This acceleration of meiosis I complements findings in mouse oocytes where, by various nocodazole incubations, the period of meiosis I most sensitive to delay by nocodazole treatment was found to be 6-8 h after NEB (Brunet et al 1999). In this study, we wanted to test whether ZM447439 would overcome a SAC arrest imposed by nocodazole.…”

“…Such a configuration allows homologous chromosomes to divide reductionally in meiosis I but sister chromatids to divide equationally in meiosis II and mitosis. A further facet of meiosis I is an extremely protracted prometaphase, lasting several hours, during which the spindle assembles for the most part without kinetochore-microtubule attachments (Brunet et al 1999).…”

Aurora B regulates spindle bipolarity in meiosis in vertebrate oocytes

“…these results suggest that in vertebrate oocytes that lack centrosomes, one major function of Aur-B is to stabilize chromosome-associated spindle microtubules to ensure spindle bipolarity. 11,12 characterized by barrel shape, with chromosomes appearing "imbedded" within the dense microtubule network and with no prominent kinetochore microtubules. Studying spindle microtubule dynamics in the presence of excess MCAK or Op18/Stathmin, another microtubule-destabilizing protein, have revealed that only 5% of microtubules are kinetochore microtubules, 13,14 and the rest belong to two functionally distinct non-kinetochore microtubules, polar array microtubules (similar to aster microtubules in mitosis) and barrel array microtubules.…”