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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD068158-03
Application #
8446115
Study Section
Special Emphasis Panel (ZHD1-DSR-L)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2013
Total Cost
$314,283
Indirect Cost
$124,854
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Fan, Qianlan; Cheng, Yuan; Chang, Hsun-Ming et al. (2017) Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling. Oncotarget 8:27166-27176
Feng, Yi; Cui, Peng; Lu, Xiaowei et al. (2017) CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions. Sci Rep 7:44810
Karakikes, Ioannis; Termglinchan, Vittavat; Cepeda, Diana A et al. (2017) A Comprehensive TALEN-Based Knockout Library for Generating Human-Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases. Circ Res 120:1561-1571
Feng, Yi; Zhu, Shoujun; Antaris, Alexander L et al. (2017) Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore. Chem Sci 8:3703-3711
Panula, Sarita; Reda, Ahmed; Stukenborg, Jan-Bernd et al. (2016) Over Expression of NANOS3 and DAZL in Human Embryonic Stem Cells. PLoS One 11:e0165268
Kawamura, Kazuhiro; Kawamura, Nanami; Hsueh, Aaron J W (2016) Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol 28:217-22
Durruthy-Durruthy, Jens; Sebastiano, Vittorio; Wossidlo, Mark et al. (2016) The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming. Nat Genet 48:44-52
Zhai, Jun; Yao, Guidong; Dong, Fangli et al. (2016) In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients. J Clin Endocrinol Metab 101:4405-4412
Cheng, Yuan; Kim, Jaehong; Li, Xiao Xiao et al. (2015) Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators. PLoS One 10:e0117769
Phadnis, Smruti M; Loewke, Nathan O; Dimov, Ivan K et al. (2015) Dynamic and social behaviors of human pluripotent stem cells. Sci Rep 5:14209

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