Regulation of the female mouse germ cell cycle during entry into meiosis


During mouse embryonic development germ cells proliferate extensively until they commit to the male or female pathway and arrest in mitosis or meiosis respectively. Whilst the transition of female germ cells exiting the mitotic cell cycle and entering meiosis is well defined histologically, the essential cell cycle proteins involved in this process have remained unresolved. Using flow cytometry we have examined the entry of female germ cells into meiosis, their termination of DNA synthesis and entry into prophase I. Analysis of key G2/M cell cycle proteins revealed that entry into meiosis and cell cycle exit at G2/M involves repression of G2/M promoting Cyclin B1, coincident upregulation of G2/M repressing Cyclin B3 and robust establishment of the ATM/CHK2 pathway. By contrast we show that the ATR/CHK1 pathway is activated in male and female germ cells. This data indicates that an important G2/M surveillance mechanism operates during germ cell proliferation and that passage into meiotic G2/M involves the combined repression of G2/M through Cyclin B3 and activation of the key G2/M checkpoint regulatory network modulated through ATM and CHK2. This work shows that the core regulatory machinery that controls G2/M progression in mitotic cells is activated in female mouse germ cells as they enter meiosis.

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Regulation of the female mouse germ cell cycle during entry into meiosis