Immune cells, which home to various bodily regions and are also recruited to injury sites, must weigh competing guidance signals to end up in the location where they will be most effective at a given time. Moreira et al. investigated the responses of migrating Drosophila hemocytes to injury to determine their prioritization of competing signals. During embryonic development, hemocytes (Drosophila macrophages) from the head follow a stereotyped migration pattern, traveling down the ventral nerve cord and then leaving the midline in a series of lateral segmental migrations. At late stage 14, injuries adjacent to the midline can divert hemocytes from their migratory pattern so that they migrate toward a nearby epithelial lesion. After using genetic and pharmacological approaches to rule out various candidate “injury signals,” Moreira et al. showed that beads grafted into the ventral epithelium (generating a wound) failed to attract hemocytes when impregnated with a drug that inhibited H2O2 production. Similarly, epidermal knockdown of the H2O2-producing enzyme Duox reduced recruitment to wounds. Hemocytes recruited to wounds 15 to 20 μm from the midline returned to the midline after resolution of the injury; although hemocytes were attracted to injuries as far as 50 μm from the midline, they failed to return to the midline after wound closure. Migrating hemocytes failed to respond to injury before late stage 14, although they did migrate to apoptotic hemocytes. The growth factors Pvf2 and Pvf3, which are abundant in the developing nerve cord, have been implicated in ventral midline migration; the early refractile period was not apparent in patches of head-region epithelium lacking these growth factors; moreover, overexpression of Pvf2 throughout the epidermis (destroying Pvf2 gradients and preventing developmental migration from the head) enabled hemocytes to respond to injuries at earlier developmental stages. The authors thus conclude that H2O2 represents the immediate wound attractant signal and that hemocytes fail to respond to injuries early in migration because they are “distracted” by developmental cues.
S. Moreira, B. Stramer, I. Evans, W. Wood, P. Martin, Prioritization of competing damage and developmental signals by migrating macrophages in the Drosophila embryo. Curr. Biol. 20, 464–470 (2010). [PubMed]