Primordial germ cells (PGCs) are set aside from other tissues in vertebrate embryos at an early stage of development. They are the founder cells of the germ line, which will give rise to all the gametes produced during the life cycle, and thus all future generations of the species concerned. Despite this central place in biology, little is known in detail about the early stages in germ cell differentiation. In this project, we wish to identify the molecular basis of PGC behavior in early mouse embryos. After they first appear, PGCs migrate through the tissues of the embryo to join the cells that will form the somatic tissues of the.gonad. This period of PGC migration is crucial. If it occurs incorrectly, or not at all, the gonads do not become populated by germ line cells, and the individual remains sterile for the rest of the lifecycle. In vertebrates, mammals included, PGC migration occurs during the rapid period of organogenesis that occurs after the basic axes of the body have been formed during gastrulation. Previous work from this laboratory has shown that many aspects of PGC behavior in mice, including their survival, migration, and proliferation, are controlled by specific growth factors. The migration of PGCs must also involve changes in PGC adhesiveness. Recently, we have used simple in vitro as says to show that this is the case. PGCs show differential changes in their adhesiveness to different purified extracellular matrix glycoproteins when tested before, during, and after their migration. We have also found that PGCs alter their adhesiveness to each other during their migration, and that PGC:POC adhesion is part of the process of assembly of the gonad. This project will focus on the control of PGC adhesiveness, both to other PGCs and to the extracellular matrix. We will use simple in vitro assays developed in our laboratory to identify the specific sites on extracellular matrix glycoproteins used by PGCs during migration and gonad assembly, as well as the adhesion molecules used for PGC aggregation during migration. As well as furthering our understanding of the biology of these fundamentally important cells, this study will provide insights into the formation of germ line tumors, as well as potential causes of infertility.
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