Mos limits the number of meiotic divisions in urochordate eggs

Abstract

SUMMARYMos kinase is a universal mediator of oocyte meiotic maturation and is produced during oogenesis and destroyed after fertilization. The hallmark of maternal meiosis is that two successive M phases (meiosis I and II) drive two rounds of asymmetric cell division (ACD). However, how the egg limits the number of meioses to just two, thereby preventing gross aneuploidy, is poorly characterized. Here, in urochordate eggs, we show that loss of Mos/MAPK activity is necessary to prevent entry into meiosis III. Remarkably, maintaining the Mos/MAPK pathway active after fertilization at near physiological levels induces additional rounds of meiotic M phase (meiosis III, IV and V). During these additional rounds of meiosis, the spindle is positioned asymmetrically resulting in further rounds of ACD. In addition, inhibiting meiotic exit with Mos prevents pronuclear formation, cyclin A accumulation and maintains sperm-triggered Ca 2+ oscillations, all of which are hallmarks of the meiotic cell cycle in ascidians. It will be interesting to determine whether Mos availability in mammals can also control the number of meioses as it does in the urochordates. Our results demonstrate the power of urochordate eggs as a model to dissect the egg-to-embryo transition.

Cuf2 boosts the transcription of APC/C activator Fzr1 to terminate the meiotic division cycle

“…The occurrence of meiosis III-like division in S. pombe revealed in this study suggests that the extra division in these species might also be assured by a mechanism to lower the APC/C activity. Meiosis III-type phenomena have been observed in mouse, bovine, plant and ascidian meioses [17][18][19][20]. In mouse and ascidian meioses, proper regulation of Mos-MAPK activity is essential to avoid the entry to meiosis III [19,21,22], although this is unlikely to be a universal mechanism according to studies in other species, including amphibians [23].…”

Meeting report – Oocyte maturation and fertilization: lessons from canonical and emerging models

“…The proteomic approach performed by Mariana Wolfner in such a genetically tractable model offers the possibility to identify the numerous actors of egg activation and validate them by knockdown of each of the proteins identified. If the pathways that involve Ca 2+ are largely conserved during Drosophila egg activation (Pesin and Orr-Weaver, 2007;Sackton et al, 2007;Yamamoto et al, 2008;Dumollard et al, 2011), the proteomic approach performed by Mariana Wolfner and other Drosophila researchers will help to shed new light on the processes that support egg activation.…”

Comparing Pig and Amphibian Oocytes: Methodologies for Aneuploidy Detection and Complementary Lessons for MAPK Involvement in Meiotic Spindle Morphogenesis

“…First evidence supporting this hypothesis was recorded in mice oocytes where maintaining MAPK activity inhibits pronucleus formation (Moos et al, 1995;Moos et al, 1996) and where entry to meiosis III is observed in the presence of high level of MAPK/Erk activity (Verlhac et al, 1996). The hypothesis that Mos-MAPK/Erk network could be the determining factor limiting the number of meiosis to two was recently formally tested in urochordates, which are at the crossroad between invertebrates and vertebrates (Dumollard et al, 2011). In ascidian eggs, prolonging MAPK activity by expressing murine Mos leads to entry into supernumerary rounds of M-phases, which was attested by the increased number of polar bodies (Dumollard et al, 2011).…”

“…The hypothesis that Mos-MAPK/Erk network could be the determining factor limiting the number of meiosis to two was recently formally tested in urochordates, which are at the crossroad between invertebrates and vertebrates (Dumollard et al, 2011). In ascidian eggs, prolonging MAPK activity by expressing murine Mos leads to entry into supernumerary rounds of M-phases, which was attested by the increased number of polar bodies (Dumollard et al, 2011). Then, urochordates offer an attractive model to unravel new observations on a conserved role of MAPK/Erk in spindle morphogenesis and to decipher the mechanisms leading to uncontrolled division and polyploidy since the successive rounds of M-phases observed in these cases occur without intervening replication.…”