Superimposed migratory paths that are travelled by haemocytes as they migrate laterally from the ventral midline in a Drosophila embryo. Image courtesy of C. Faria and W. Wood, Instituto de Medicina Molecular, Lisbon, Portugal.
Before a fly can first flap its wings, its haemocytes are already efficient travellers. Haemocyte migration occurs as a crucial part of embryogenesis and as a response to tissue damage or pathogenic threats. But is migration always mediated by the same mechanism? Tackling this question, Jacinto, Wood and colleagues report in The Journal of Cell Biology that at least two distinct pathways mediate haemocyte localization in Drosophila melanogaster.
Haemocyte distribution originates in the head mesoderm at stage 10 of embryogenesis, and follows a regular migration route along the ventral midline until the entire embryo is populated by stage 17. A rigorous study of migrating haemocytes by Wood et al., using live time-lapse imaging, showed that haemocytes begin to cluster along the ventral midline at stage 14, and move laterally from these ventral clusters at defined exit points between stages 14–16.
It has already been established that the PDGF/VEGF receptor ligands (PVF1–3) function redundantly as chemotactic signals in haemocyte dispersal. Now, Wood et al. have shown that the pattern of PVF2 and PVF3 expression mimics the pattern of haemocyte migration in the ventral midline. Furthermore, double inactivation of PVF2 and PVF3 by RNA interference resulted in the loss of haemocyte migration in this region, and the overexpression of PVF2 resulted in reduced lateral migration of haemocytes during embryonic stages 14–16. However, the in vivo expression of an inactive form of phosphatidylinositol 3-kinase (PI3K; a protein that mediates cell migration in other systems) did not affect haemocyte migration.
In a second set of experiments, the authors explored haemocyte response to laser-ablation and bead-implantation-induced damage. The process of bead-implantation, which was adapted by the authors from a chick developmental biology technique, involves the insertion of heparin beads into D. melanogaster embryos with a tungsten needle. Under wild-type conditions, fly haemocytes quickly aggregated around both types of wound. Also, PVF-receptor mutant flies had a normal haemocyte migration response after laser ablation. By contrast, haemocytes were not recruited to laser or bead-induced damage sites after the expression of the inactive form of PI3K or after the inactivation of PI3K by inhibitors.
So, haemocyte dispersal during development is regulated by the chemotactic signalling of PVF ligands and receptors. Wound response, however, is mediated by PI3K signalling. The authors note that these different pathways operate, not surprisingly, at different speeds. Developmental migration does not require speed, but demands even and correct cell dispersal. On the other hand, chemotaxis towards a wound must be fast, as it is needed for an immediate response to acute threats to the organism — including those that are caused by a fly's first, bumpy landings.