Primordial germ cells are the founder cells of the gametes. They arise early in development and migrate to the sites of gonad formation, where they combine with somatic cells to form the primary sex cords. These are the forerunners of the seminiferous tubules in males, and the ovarian follicles in females. This project aims to study the molecular basis of primordial germ cell migration, and assembly of the sex cords. During the initial funding period of this grant, we have developed tools to study the roles of individual cell surface molecules expressed by primordial germ cells as they migrate, including making a strain of mice that expresses green fluorescent protein in the germ cells. This has allowed, for the first time, direct observation of migrating primordial germ cells in living embryos, as well as a means of purifying them for biochemical analysis. Using these, we have identified receptors of the integrin family expressed by primordial germ cells, and carried out genetic studies of their roles in germ cell migration. We find that beta1 integrin is required for normal migration of the germ cells to the gonad primordia. We now wish to extend this analysis to other receptors expressed by germ cells, including cell surface proteoglycans and growth factor receptors. In addition, we aim to use the advantage of the green fluorescent protein marker to study the mechanism of germ cell locomotion, and its control, in the living embryo. These studies will provide new insight into the formation of the mammalian gonad, the basis of germ cell tumors, and the migration of early embryonic cells.
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