Netrin-G1 Regulates Microglial Accumulation along Axons and Supports the Survival of Layer V Neurons in the Postnatal Mouse Brain

Abstract

Summary: Microglia, the resident immune cells of the central nervous system, accumulate along subcerebral projection axons and support neuronal survival during the early postnatal period. It remains unknown how microglia follow an axon-specific distribution pattern to maintain neural circuits. Here, we investigated the mechanisms of microglial accumulation along subcerebral projection axons that were necessary for microglial accumulation in the internal capsule. Screening of molecules involved in this accumulation of microglia to axons of layer V cortical neurons identified netrin-G1, a member of the netrin family of axon guidance molecules with a glycosyl-phosphatidylinositol anchor. Deletion or knockdown of the netrin-G1 gene Ntng1 reduced microglial accumulation and caused loss of cortical neurons. Netrin-G1 ligand-Ngl1 knockout-mice-derived microglia showed reduced accumulation along the axons compared with wild-type microglia. Thus, microglia accumulate around the subcerebral projection axons via NGL1-netrin-G1 signaling and support neuronal survival. Our observations unveil bidirectional neurotrophic interactions between neurons and microglia. : The mechanism underlying microglial accumulation along subcerebral projection axons to maintain neural circuits during the early postnatal period remains largely unknown. Fujita et al. demonstrate that microglial NGL1 and neuronal netrin-G1 signaling mediates microglial accumulation around the subcerebral projection axons and supports neuronal survival. Keywords: brain, microglia, neuron, axon, netrin-G1