Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone

Abstract

Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1β signaling; interleukin-1 receptor inhibition rescues precursor proliferation invivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ.