The goal of our research is to identify molecular mechanisms that regulate the development of primordial germ cells (PGCs). PGCs are transient stem cells in the embryo that give rise to either male or female gametes. Since their origin is distinct from that of the gonad, PGCs must traverse the growing embryo to reach the nascent ovaries or testes, where differentiation as eggs or sperm ensues. Successful reproduction of the adult depends upon proper development of PGCs: their establishment, migration, and proliferation. Throughout these events, PGCs must maintain the potential to produce an entirely new organism in a few subsequent cell divisions; failures in such maintenance can result in loss of fertility, whereas the failure to restrict this potential to PGCs can result in germ cell tumors. Enhancing our now rudimentary molecular understanding of PGC development may provide insights into infertility and cancer as well as manipulating and maintaining pluripotent stem cells in vitro.
We are using the emerging strength of genetics in the mouse to study the machinery of self-renewal, migration, and regulation of PGCs in vivo. In order to discover new genes involved in PGC development, we have screened randomly mutagenized mouse embryos and isolated eight recessive mutants with PGC defects. By identifying the affected gene and characterizing the embryonic and adult consequences of its mutation, we will attain a broader understanding of the genetic pathways that regulate PGC development. In tandem, we are creating new strains of transgenic mice that will facilitate the characterization of our collection of PGC mutants as well as providing tools for the study of normal and diseased PGCs.