On the transition from the meiotic to mitotic cell cycle during early mouse development

Abstract

Here, we outline the mechanisms involved in the regulation of cell divisions during oocyte maturation and early cleavages of the mouse embryo. Our interest is focused on the regulation of meiotic M-phases and the first embryonic mitoses that are differently tuned and are characterized by specifically modified mechanisms, some of which have been recently identified. The transitions between the M-phases during this period of development, as well as associated changes in their regulation, are of key importance for both the meiotic maturation of oocytes and the further development of the mammalian embryo. The mouse is an excellent model for studies of the cell cycle during oogenesis and early development. Nevertheless, a number of molecular mechanisms described here were discovered or confirmed during the study of other species and apply also to other mammals including humans. KEY WORDS: meiosis, mitosis, oocyte, embryo, MPF, CSF, spindle assembly checkpoint, Mad2, Rec8Cell cycle is often modified in different cell types during development and aging of the individual. These adaptations seem to be of a particular importance for the success of the early developmental program. The cell cycle must be modified during meiosis, when DNA replication is suppressed, during spermatogenesis in males and in oocytes undergoing the process of meiotic maturation in females. The oocyte enters the first meiotic prophase that can take several years. Then, in sexually mature females, the oocyte resumes meiosis and progress through two M-phases of the meiotic maturation, each of them differently regulated, to assure correct separation of maternal chromatin. Fertilized egg transits from meiotic to the mitotic cell cycle and resume DNA replication.In the current review we will focus on M-phase modifications that are the subject of the research in our laboratories. We choose three examples of specific M-phase adjustments i.e. metaphase I, and metaphase II of oocyte meiotic divisions and the first mitosis of mouse embryo. We center our attention on the temporal regulation of metaphase I progression and the singularities of the spindle assembly checkpoint during this period, mechanisms of sustaining and exiting metaphase II-arrest, and finally the unique regulation of the first embryonic mitosis. The correct timing of Int.

Spindle assembly checkpoint-related failure perturbs early embryonic divisions and reduces reproductive performance of LT/Sv mice

“…Therefore, the LT/Sv phenotype both in oocytes and embryos might comprise only meiotic elements of the cell-cycle control. Previous findings from our laboratories suggest that some meiotic pathways are functional also during the earliest cell-cycles of dividing embryos (Kubiak et al 2008c). Thus, in LT/Sv mice, the defective meiotic elements of cell-cycle regulation could affect the SAC pathway not only during meiosis but also during the earliest embryonic divisions.…”

“…However, mitotic and meiotic cellular environments differ significantly and modify SAC action. Most importantly, in oocytes, in contrast to embryos, the MOS/./EMI2 (FBXO43) pathway inhibits APC/C in a similar way as does the SAC (Kubiak et al 2008c). This results in a doubled system of APC/C inhibition upon MII arrest.…”

“…Last but not the least, certain discrete similarities in regulation of the M-phases in oocytes (MPF activation/inactivation and related phenomena as M-phase duration or cytoskeleton activities) and one-cell and two-cell embryos were also reported (Ciemerych et al 1999, Kubiak & Ciemerych 2001, Sikora-Polaczek et al 2006. Therefore, the first mitotic cell cycle (and perhaps subsequent ones) is governed by specific mechanisms transitional between meiotic and mitotic type of cellcycle regulation (Kubiak et al 2008a(Kubiak et al , 2008b(Kubiak et al , 2008c.…”

“…The cell-cycle regulation of mouse oocytes and onecell embryos shares several similarities (Kubiak et al 2008c). Both the meiotic maturation of the mouse oocyte and the first embryonic cell cycle occur in the absence of transcription, i.e., under the control of maternal factors accumulated during oocyte growth (Oh et al 2000, Wang et al 2004, with exception to certain rare transcripts appearing in the late zygote (Ram & Schultz 1993, Bouniol et al 1995.…”

Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach

“…inactivation has been proposed earlier (Watanabe et al, 1991). Such a pathway is indeed necessary to account for some experimental observations, as the possible arrest of mammalian eggs in metaphase III, a pathological state resulting from an incomplete activation of the egg (Kubiak et al, 2008) or the fact that the decrease in MPF activity following one Ca 2+ spike is only transient (Collas et al, 1995). As there is no synthesis of CSF in metaphasearrested eggs, a transient activation of APC can only be explained by the existence of another pathway.…”