Microglia Maintain Homeostatic Conditions in the Developing Rostral Migratory Stream

Microglia invade the neuroblast migratory corridor of the rostral migratory stream (RMS) early in development. The early postnatal RMS does not yet have the dense astrocyte and vascular scaffold that helps propel for-ward migrating neuroblasts, which led us to consider whether microglia help regulate conditions permissive to Significance Statement Microglia are brain-resident immune cells responsible for maintaining homeostatic conditions necessary for normal neurodevelopment. Microglia phagocytosis is essential during critical periods of development to clear the results of over-exuberant neurogenesis, while microglia-expressed growth factors provide trophic support. Microglial activities may be of special relevance to the olfactory system, which is unique for both a prolonged period of neurogenesis and increased immunologic threat. This work examines how microglia maintain homeostatic conditions in the neuroblast migratory corridor of the rostral migratory stream (RMS) in the olfactory system during early postnatal development. Our findings illustrate the importance of micro-glia in promoting an environment that allows for effective neuroblast migration in the RMS and has implica-tions for neuroblast migration elsewhere in the nervous system. neuroblast migration in the RMS. GFP-labeled microglia in CX3CR-1GFP/+ mice assemble primarily along the outer borders of the RMS during the first postnatal week, where they exhibit predominantly an ameboid mor-phology and associate with migrating neuroblasts. Microglia ablation for 3 d postnatally does not impact the density of pulse labeled BrdU+ neuroblasts nor the distance migrated by tdTomato electroporated neuro-blasts in the RMS. However, microglia wrap DsRed-labeled neuroblasts in the RMS of P7 CX3CR-1GFP/+; DCXDsRed/+ mice and express the markers CD68, CLEC7A, MERTK, and IGF-1, suggesting active regulation in the developing RMS. Microglia depletion for 14 d postnatally further induced an accumulation of CC3+ DCX+ apoptotic neuroblasts in the RMS, a wider RMS and extended patency of the lateral ventricle extension in the olfactory bulb. These findings illustrate the importance of microglia in maintaining a healthy neuroblast popula-tion and an environment permissive to neuroblast migration in the early postnatal RMS.