Microglia promote the proliferation of neural precursor cells by secreting osteopontin.

Microglia are central nervous system-resident immune cells that play a crucial role in brain development by interacting with neural precursor cells (NPCs). It has been reported that microglia regulate the number of NPC by phagocytosis, inducing apoptosis, and promoting proliferation. Microglia surrounding the subventricular zone express osteopontin (OPN) during brain development. The present study investigated the role of microglia in proliferation of NPCs in vitro, and identified the OPN receptor critical for proliferation of NPCs. Microglia co-cultured with NPCs in the presence of an OPN-neutralizing antibody resulted in OPN inhibition and reduced microglia-induced proliferation of NPCs. NPCs express integrin αvβ3, which has been identified as an OPN receptor. Cilengitide, an inhibitor of integrin αvβ3, also inhibited microglia-induced proliferation of NPCs. These results suggest that microglia promote the proliferation of NPCs via OPN-integrin αvβ3 signaling.