PROJECT 2: Translational Regulation of Meiotic Cell Cycle Onset & Progession in

Stanford University, Stanford CA

Investigators

Linked publications, trials & patents

Abstract

Meiosis is the signature event of the germ cell developmental program, absolutely required for sexual reproducfion eukaryotes. Proper regulafion of meiotic progression is crucial for producfion of funcfional 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 greafiy extended G2, termed meiofic prophase, prior to the two meiotic divisions. This signature cell cycle delay provides critical fime 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 eariy embryogenesis are largely accomplished during meiofic prophase. In male germ cells, although dramafic morphological changes that produce mature gametes occur after the meiofic 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 acfivafion 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 crifical control circuits that first pause the cell cycle, then finally acfivate the G2/M transition for meiosis I once proper expression of the program for gametogenesis has been achieved.