Putting Out the Welcome Mat: Chemical guides germ cells to gonads

Even though it only covers a few millimeters, the trip can take several days. In the mouse embryo, cells that spawn sperm or eggs must travel from where they arise to their destination in the developing gonads.

A Japanese research team has now identified a chemical signal that enables these primordial germ cells to hone in on the gonads. The discovery mirrors recent findings in fish embryos, making it likely that the same guidance mechanism works in human embryos, as well.

In mice, the chemical lure for primordial germ cells is a protein known as stromal cell-derived factor-1 (SDF-1), Takashi Nagasawa of Kyoto University in Japan and his colleagues report in an upcoming Proceedings of the National Academy of Sciences. They and other researchers had already determined that SDF-1, a chemical signal known as a chemokine, guides the migration of nerve cells in the brain and of cells that form blood vessels.

Hypothesizing that SDF-1 also influences the movement of primordial germ cells, Nagasawa’s team studied a mutant strain of mice unable to make the chemokine. Although these mice die as embryos, they live beyond the time when the gonads of normal mice are colonized by primordial germ cells.

Nagasawa and his colleagues found that while the germ cells do migrate through the mutant embryo, fewer than half the normal number of these cells end up in the gonads. The scientists have also found that in normal mice, SDF-1 is produced in a ridge of gonadal cells and that mouse primordial germ cells sport a protein called CXCR4 that detects the chemokine.

Fish versions of SDF-1 and CXCR4 are critical for the migration of primordial germ cells, other researchers reported in the Nov. 27, 2002 Cell and the Jan. 16 Nature. In zebrafish embryos lacking the key chemokine, for example, the germ cells disperse randomly instead of heading for the gonads.

“In the mouse, SDF-1 appears to be required for the execution of the last step when the cells colonize the genital ridge which expresses the chemokine,” says Erez Raz of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, who led the Cell study. “In the case of the zebrafish, the cells appear to depend on the chemokine throughout their migration and not just at the last step.”

Although it would be difficult, if not impossible, to confirm that SDF-1 guides the migration of primordial germ cells in a human embryo, Nagasawa says that his group will study whether human primordial germ cells make the chemokine’s receptor. Raz suggests that such work could provide insight into rare childhood cancers that may originate from primordial germ cells gone astray.


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