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First published online August 4, 2003
doi: 10.1242/10.1242/dev.00640
1 Division of Developmental Biology, Children's Hospital Research Foundation,
Cincinnati, OH 45229, USA
2 Developmental Genetics Program, Skirball Institute of Biomolecular Medicine,
New York University Medical Center and Howard Hughes Medical Institute, New
York, NY 10016, USA
3 Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077
Gottingen, Germany
4 Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine,
New York University Medical Center and Howard Hughes Medical Institute, New
York, NY 10016, USA
Authors for correspondence (e-mail:
Lehmann{at}saturn.med.nyu.edu
and
Christopher.Wylie{at}chmcc.org)
Accepted 29 May 2003
In mouse embryos, germ cells arise during gastrulation and migrate to the early gonad. First, they emerge from the primitive streak into the region of the endoderm that forms the hindgut. Later in development, a second phase of migration takes place in which they migrate out of the gut to the genital ridges. There, they co-assemble with somatic cells to form the gonad. In vitro studies in the mouse, and genetic studies in other organisms, suggest that at least part of this process is in response to secreted signals from other tissues. Recent genetic evidence in zebrafish has shown that the interaction between stromal cell-derived factor 1 (SDF1) and its G-protein-coupled receptor CXCR4, already known to control many types of normal and pathological cell migrations, is also required for the normal migration of primordial germ cells. We show that in the mouse, germ cell migration and survival requires the SDF1/CXCR4 interaction. First, migrating germ cells express CXCR4, whilst the body wall mesenchyme and genital ridges express the ligand SDF1. Second, the addition of exogenous SDF1 to living embryo cultures causes aberrant germ cell migration from the gut. Third, germ cells in embryos carrying targeted mutations in CXCR4 do not colonize the gonad normally. However, at earlier stages in the hindgut, germ cells are unaffected in CXCR4-/- embryos. Germ cell counts at different stages suggest that SDF1/CXCR4 interaction also mediates germ cell survival. These results show that the SDF1/CXCR4 interaction is specifically required for the colonization of the gonads by primordial germ cells, but not for earlier stages in germ cell migration. This demonstrates a high degree of evolutionary conservation of part of the mechanism, but also an area of evolutionary divergence.
Key words: PGCs, SDF1, CXCR4, Chemokine, Migration, Mouse
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