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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG2-HED-2 (01))
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University of Minnesota Twin Cities
Schools of Medicine
United States
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Runyan, Christopher; Schaible, Kyle; Molyneaux, Kathleen et al. (2006) Steel factor controls midline cell death of primordial germ cells and is essential for their normal proliferation and migration. Development 133:4861-9
Takeuchi, Yutaka; Molyneaux, Kathleen; Runyan, Chris et al. (2005) The roles of FGF signaling in germ cell migration in the mouse. Development 132:5399-409
Stebler, Jurg; Spieler, Derek; Slanchev, Krasimir et al. (2004) Primordial germ cell migration in the chick and mouse embryo: the role of the chemokine SDF-1/CXCL12. Dev Biol 272:351-61
Molyneaux, Kathleen A; Wang, Ying; Schaible, Kyle et al. (2004) Transcriptional profiling identifies genes differentially expressed during and after migration in murine primordial germ cells. Gene Expr Patterns 4:167-81
Molyneaux, Kathleen A; Zinszner, Helene; Kunwar, Prabhat S et al. (2003) The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development 130:4279-86
Molyneaux, Kathleen A; Schaible, Kyle; Wylie, Christopher (2003) GP130, the shared receptor for the LIF/IL6 cytokine family in the mouse, is not required for early germ cell differentiation, but is required cell-autonomously in oocytes for ovulation. Development 130:4287-94
Stallock, James; Molyneaux, Kathy; Schaible, Kyle et al. (2003) The pro-apoptotic gene Bax is required for the death of ectopic primordial germ cells during their migration in the mouse embryo. Development 130:6589-97
Anderson, O; Heasman, J; Wylie, C (2001) Early events in the mammalian germ line. Int Rev Cytol 203:215-30
Molyneaux, K A; Stallock, J; Schaible, K et al. (2001) Time-lapse analysis of living mouse germ cell migration. Dev Biol 240:488-98
Bendel-Stenzel, M R; Gomperts, M; Anderson, R et al. (2000) The role of cadherins during primordial germ cell migration and early gonad formation in the mouse. Mech Dev 91:143-52

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