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A zebrafish homologue of the chemokine receptor Cxcr4 is a germ-cell guidance receptor

Abstract

Germ cells preserve an individual's genetic information and transmit it to the next generation. Early in development germ cells are set aside and undergo a specialized developmental programme, a hallmark of which is the migration from their site of origin to the future gonad1. In Drosophila, several factors have been identified that control germ-cell migration to their target tissues2,3,4; however, the germ-cell chemoattractant or its receptor have remained unknown. Here we apply genetics and in vivo imaging to show that odysseus, a zebrafish homologue of the G-protein-coupled chemokine receptor Cxcr4, is required specifically in germ cells for their chemotaxis. odysseus mutant germ cells are able to activate the migratory programme, but fail to undergo directed migration towards their target tissue, resulting in randomly dispersed germ cells. SDF-1, the presumptive cognate ligand for Cxcr4, shows a similar loss-of-function phenotype and can recruit germ cells to ectopic sites in the embryo, thus identifying a vertebrate ligand–receptor pair guiding migratory germ cells at all stages of migration towards their target.

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Figure 1: ody affects PGC positioning and is required within the germ line.
Figure 2: PGC migration in wild-type and ody mutant embryos.
Figure 3: The G-protein-coupled chemokine receptor Cxcr4b is required for PGC guidance in zebrafish.
Figure 4: SDF-1 is a chemoattractant for PGCs.

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Acknowledgements

We thank F. Schnorrer for discussions and critical comments on the manuscript. The PH–GFP fusion protein was a gift from M. Landree and P. Devreotes. H.K. was in part supported by a Boehringer Ingelheim predoctoral fellowship. R.G. was supported by the German Human Genome Project (DHGP). This work was supported by the Max-Planck Gesellschaft. Publication costs were in part defrayed by the Fonds der Chemischen Industrie.

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Correspondence to Holger Knaut.

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Knaut, H., Werz, C., Geisler, R. et al. A zebrafish homologue of the chemokine receptor Cxcr4 is a germ-cell guidance receptor. Nature 421, 279–282 (2003). https://doi.org/10.1038/nature01338

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