Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of sharedreceptor

The dynamic and coordinated interaction between cells and their microenviro nment controls cell migration, proliferation, and apoptosis, mediated by di fferent cell surface molecules. We have studied the response of a neuroecto dermal progenitor cell line, Dev, to a guidance molecule, semaphorin 3A (Se ma3A), described previously as a repellent-collapsing signal for axons, and we have shown that Sema3A acts as a repellent guidance cue for migrating p rogenitor cells and, on prolonged application, induces apoptosis. Both repu lsion and induction of cell death are mediated by neuropilin-1, the ligand- binding component of the Sema3A receptor. The vascular endothelial growth f actor, VEGF165, antagonizes Sema3A-induced apoptosis and promotes cell surv ival, migration, and proliferation. Surprisingly, repulsion by Sema3A also depends on expression of VEGFR1, a VEGF165 receptor, expressed in Dev cells . Moreover, we found that these repulsive effects of Sema3A require tyrosin e kinase activity, which can be attributed to VEGFR1. These results indicat e that the balance between guidance molecules and angiogenic factors can mo dulate the migration, apoptosis (or survival), and proliferation of neural progenitor cells through shared receptors.