The active migration of bloodcells, or hemocytes, occurs during fly embryogenesis when the heart has not yet begun pumping. Fly blood does not travel through a closed circulatory system, but Cho found that flies have homologues of the VEGF pathway, which is required for vertebrate blood vessel development. This suggests that the proteins have a more ancient function.
That function appears to be the migration of blood cells during embryogenesis, according to the new study. Cho and colleagues found that, in flies lacking VEGFR, blood cells differentiate, but do not migrate normally and aggregate in the anterior of the embryo. Inactivation of all three homologues of the VEGF ligand resulted in the same cell migration defect. Ectopic expression of a VEGF ligand caused misrouting of blood cells, suggesting that it may act as a chemoattractant to assure that the hemocytes travel along pathways where phagocytosis of apoptotic cells is required.
Blood cell chemoattractant activity has also been demonstrated in vitro for a vertebrate VEGF, but has largely been ignored. “While most of the press for VEGF involves its role in angiogenesis…it may have originally evolved for blood cell functions,” says Cho. However, it is not known whether the vertebrate homologues still serve similar functions in blood cells. The simple genetics of the fly system should facilitate the identification of signaling molecules downstream of VEGF, which may aid in the discovery of therapeutic agents for blocking angiogenesis during tumor growth or increasing vascular growth after injuries such as heart attack. ▪