Sexual reproduction of multicellular organisms depends critically on communication between cells of the somatic gonad and the germ line, and ultimately between sperm and egg. In many species, intercellular signaling plays a pivotal role in coordinating meiosis and fertilization: developing oocytes arrest at diakinesis for prolonged periods and resume meiosis (meiotic maturation) in response to hormones. Meiotic maturation is defined by the transition between diakinesis and metaphase of meiosis I and is accompanied by nuclear envelope breakdown, cortical cytoskeletal rearrangement, and meiotic spindle assembly. There is an acute need for information on how intercellular signals control meiotic progression because chromosome missegregation in female meiosis I is the leading cause of Down syndrome and miscarriage. The nematode Caenorhabditis elegans has emerged as a paradigm for studying meiosis and germline proliferation and their regulation by conserved signaling pathways. Our studies demonstrate that C. elegans sperm export the major sperm protein (MSP) to trigger oocyte MAP kinase activation and meiotic maturation. In the prior funding period, we discovered that somatic G1s and G1o/i signaling pathways function in parallel with the MSP/Eph receptor to regulate meiotic maturation. Our genetic data implicate gap-junctional communication between oocytes and somatic cells of the gonad as a critical target of MSP signaling. Genetic analysis also uncovered a broader role for sperm signals and gap-junctional communication in regulating the actomyosin-dependent cytoplasmic streaming that drives oocyte growth. Soma-germline interactions play many essential roles during reproduction, yet much remains to be learned about their underlying mechanistic basis, hence we will: 1) Define the molecular composition of sheath/oocyte gap junctions;2) Test the hypothesis that MSP signaling targets inhibitory sheath/oocyte gap junctions to promote meiotic maturation;and 3) Analyze roles for MSP signaling, gap-junctional communication, and Notch signaling in coordinating oocyte growth and meiotic maturation. These studies will define the normal signaling mechanisms controlling late events in oogenesis and provide insights into how they may go awry when signaling is perturbed. Since intercellular signaling and cell cycle control mechanisms are evolutionarily conserved, studies in genetic model systems will provide crucial information on the underlying causes of meiotic errors in humans.

Public Health Relevance

Prior work has established a link between the origin of meiotic errors in oocytes and aberrant regulation of hormonal signaling in the aging ovarian microenvironment. This maternal-age effect represents the major barrier to human fertility and is the chief cause of human birth defects. Because of the extensive evolutionary conservation of developmental mechanisms, these studies in C. elegans will define the signaling mechanisms controlling late events in oogenesis and provide insights into how they may go awry when signaling is perturbed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057173-13
Application #
8299032
Study Section
Special Emphasis Panel (ZRG1-EMNR-A (02))
Program Officer
Haynes, Susan R
Project Start
1998-05-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
13
Fiscal Year
2012
Total Cost
$308,244
Indirect Cost
$95,562
Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Starich, Todd A; Hall, David H; Greenstein, David (2014) Two classes of gap junction channels mediate soma-germline interactions essential for germline proliferation and gametogenesis in Caenorhabditis elegans. Genetics 198:1127-53
Spike, Caroline A; Coetzee, Donna; Eichten, Carly et al. (2014) The TRIM-NHL protein LIN-41 and the OMA RNA-binding proteins antagonistically control the prophase-to-metaphase transition and growth of Caenorhabditis elegans oocytes. Genetics 198:1535-58
Oldenbroek, Marieke; Robertson, Scott M; Guven-Ozkan, Tugba et al. (2013) Regulation of maternal Wnt mRNA translation in C. elegans embryos. Development 140:4614-23
Cheng, Hua; Govindan, J Amaranath; Greenstein, David (2008) Regulated trafficking of the MSP/Eph receptor during oocyte meiotic maturation in C. elegans. Curr Biol 18:705-14