Meiosis is the signature event of the germ cell developmental program, absolutely required for sexual reproduction eukaryotes. Proper regulation of meiotic progression is crucial for production of functional gametes. A key aspect of meiosis is a germ cell specific cell cycle, in which a final round of DNA synthesis (premeiotic S) is followed by a greatly extended G2, termed meiotic prophase, prior to the two meiotic divisions. This signature cell cycle delay provides critical time for homologous chromosomes to pair, synapse and recombine, as well as for major biosynthetic events that drive gamete differentiation. In oocytes, the transcriptional, translational and morphogenetic changes that produce the egg and prepare for early embryogenesis are largely accomplished during meiotic prophase. In male germ cells, although dramatic morphological changes that produce mature gametes occur after the meiotic divisions, a major part of the gene expression program that sets up spermiogenesis takes place during meiotic prophase. In both sexes, meiotic onset, progression, maturation, and activation of the meiotic divisions are key regulatory points. Understanding how these events are regulated is key for understanding the molecular basis of meiotic arrest infertility, for designing effective strategies for differentiating germ cells from embryonic precursors, and for developing and maturing competent gametes in vitro. The analysis proposed in this subproject of the U54 Cooperative Center for Reproductive and Stem Cell Biology will elucidate fundamental mechanisms that control the cell cycle for meiotic prophase, including the critical control circuits that first pause the cell cycle, then finally activate the G2/M transition for meiosis I once proper expression of the program for gametogenesis has been achieved.
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