Primordial germ cells (brown) require repulsion to get to their destination.

Primordial germ cells (PGCs) arise in a single cluster and then migrate to the two gonads during embryogenesis. Sano et al. (page 675) find that in flies the previously known guidance factors are not required for the process. Rather, a lipid phosphate phosphatase that is expressed in the central nervous system (CNS) repels the migrating PGCs, pushing them along their proper route.

Previous work using fixed material showed the general path that the PGCs take as they move to the gonad. However, the process itself has been hard to piece together from still images.

Using videomicroscopy, Sano et al. saw that the PGCs leave the gut, moving from the middle of the embryo where they are formed. The cells travel up toward the dorsal side, where the CNS is, and then laterally toward the prospective gonads. The PGCs never cross the midline of the embryo. Once a cell starts toward one side it does not move to the other.

Mutations in previously identified attractants expressed by the immature gonads had no effect on lateral migration. Nor was there an effect from mutations in CNS-expressed genes whose products are known to repel growing axons from the midline. However, in embryos lacking the wunen and wunen-2 genes, which encode lipid phosphate phosphatases expressed by the CNS, the PGCs became lost, sometimes crossing the midline and venturing into the epidermis, where they do not usually go.

The team hypothesizes that the lipid phosphate phosphatases destroy some attractant on the surface of some of the embryonic cells, thus creating a gradient or pattern that helps guide the PGCs along their path.

Remarkably, PGCs that get caught between the two stripes of wunen/wunen-2 expression, which flank the CNS, die. That observation may underscore just how important it is for primordial germ cells not to be left in the midline, and may hint at the origins of teratomas, which are rare tumors that crop up in adolescents and often occur near the midline.