Male Germ Cell Genetics
Mitch Eddy, Ph.D.
Tel (919) 541-3015
Fax (919) 541-3800
email@example.com P.O. Box 12233
Mail Drop C4-01
Research Triangle Park, North Carolina 27709
The Gamete Biology Group examines germ cell-specific genes encoding proteins essential for the structure and function of spermatogenic cells.
Male germ cell development is essential to the survival of the species and serves a fundamental role in the genetics and evolution of organisms. It involves a combination of unique processes that include meiosis, recombination, haploid gene expression, formation of the acrosome and flagellum, and condensation of the chromatin. The result is a highly specialized cell with a singular purpose. The Gamete Biology Group is identifying germ cell-specific genes encoding proteins essential for the structure and function of spermatogenic cells and defining the roles in these proteins in the development and function of male gametes. Over 2000 novel genes are expressed in male germ cells and many encode proteins required for the development or function of the male gamete.
Current studies focus on proteins associated with the fibrous sheath, ATP synthesis by glycolysis in sperm and the process of meiosis. The fibrous sheath is a novel cytoskeletal structure in the sperm flagellum and protein kinase A (PKA) anchoring protein 4 (AKAP4) is a major component. A conditional mutant of the X-linked gene for Akap4 showed that AKAP4 has a major structural role and anchors key enzymes of the glycolytic pathway. Genes for three of these enzymes, GAPDHS, PGK2 and LDHC, are spermatogenic cell-specific orthologues of ubiquitously expressed genes. Studies by group members and collaborators have shown that disruption of any of these genes severely compromises sperm motility, indicating that glycolysis is the main source of ATP in spermatozoa.
Two important steps in meiosis I are the prophase to metaphase transition and the metaphase to anaphase transition. The first transition was blocked when group members disrupted the gene for HSPA2, a chaperone and spermatogenic cell-specific member of the heat-shock 70 protein family. HSPA2 was found to be required for CDC2 and cyclin B1 dimerization to form the maturation promoting factor (MPF). Group members have generated conditional mutations in the genes for both proteins and are characterizing the phenotype produced when either protein is absent during meiosis I. The metaphase to anaphase transition requires activation of Cdc20, a component of the anaphase-promoting complex/cyclosome (APC). A novel Cdc20-binding protein, speriolin, was identified in spermatogenic cells and localized to the centrioles in spermatocytes and in the connecting piece in the sperm neck. Group members and collaborators currently are determining the phenotype produced by disruption of the gene for Spatc1 and for its binding partner Tzip1.
Major areas of research:
Mitch Eddy, Ph.D., leads the Gamete Biology Group within the Laboratory of Reproductive and Developmental Toxicology. He received his Ph.D. in 1967 at University of Texas–Galveston and further training as a Postdoctoral Fellow at Harvard Medical School. He was a Professor at the University of Washington School of Medicine before joining NIEHS in 1983.