PI3K is needed for hemocytes (green) to migrate to a wound.

During fly development, macrophage-like cells called hemocytes move along a stereotyped migration route relying on PDGF chemotactic ligands. Yet, in response to injury in embryos, hemocytes require phosphoinositide-3 kinase (PI3K) signaling for chemotaxis, report Wood et al. on page 405. The reliance on PI3K suggests that hemocytes are a better model system than previously thought for studying mammalian cell chemotactic behavior.

During embryogenesis, GFP-labeled hemocytes migrated normally in wild-type embryos, but failed to distribute properly in mutants lacking PDGF ligands. However, the cells moved normally toward wounds in both types of flies, indicating that PDGF signaling was not required for the immune response.

By contrast, hemocytes in flies lacking a functional catalytic subunit of PI3K migrated normally during development but failed to infiltrate a wound. Moreover, localized administration of a PI3K inhibitor at a wound blocked hemocyte migration.

The use of two different mechanisms for chemotaxis by hemocytes may partially explain why the cells move much more quickly in response to wounding than during development. As fly hemocytes and mammalian neutrophils share the use of PI3K during migration, Wood et al. are planning to combine fly genetics and whole organism imaging to uncover other molecular components involved in chemotaxis and wound responses.