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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD033440-09
Application #
6641212
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Tasca, Richard J
Project Start
1995-09-01
Project End
2004-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
9
Fiscal Year
2003
Total Cost
$266,514
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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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