Tre1 says when, and where, to go

For migrants heading out on a journey, it's not enough to just pull up their stakes—they need to know where they're going. According to Kunwar et al., migrating germ cells take their cues from the G protein–coupled receptor Tre1, which not only loosens the cells' ties to home, but also points them in the right direction.

Drosophila germ cells arise next to the endoderm, but must migrate through the developing midgut to reach their final destination in the gonads. The researchers had previously shown that Tre1 (“trapped in endoderm”) was essential for this transepithelial migration, but not for general cell motility, suggesting it might play a specific role at the start of migration.

Here, using live cell imaging, the team showed that when Tre1 function was lost, the cells remained in a disorganized clump at the endoderm and failed to assume the polarized shape characteristic of normal migrating cells. This mutant phenotype could be recapitulated by mutating G proteins, confirming that Tre1's role in migration was through its known function as a canonical G protein–coupled receptor.

So, was Tre1's role to start migration or to set up polarization? In fact, it was both. Tre1 signaling led to concentration of certain proteins towards the tail end of the cell, including Rho1, whose relocation had been implicated in germ cell migration, and E-cadherin. In Tre1 mutant cells E-cadherin remained at the cell periphery and kept germ cells attached to their neighbors. The authors wondered if this failure to separate from neighboring cells might account by itself for the loss of migratory ability. But by disabling cadherin in the mutant cells to loosen cell–cell adhesion, the team observed that germ cells dispersed randomly, but did not to move in an orderly way through the epithelium. “There is more to migration than the down-regulation of cadherin,” concludes Ruth Lehmann, who led the study. “It requires polarization, and Tre1 appears to organize it.”