Microglia maintain homeostatic conditions in the developing rostral migratory stream

Abstract

ABSTRACTMicroglia invade the neuroblast migratory corridor of the rostral migratory stream (RMS) early in development. This work examines how microglia maintain the homeostatic conditions permissive to neuroblast migration in the RMS during the early postnatal period. 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 morphology and associate with migrating neuroblasts. Microglia ablation for 3 days postnatally does not impact the density of pulse labeled BrdU+ neuroblasts nor the distance migrated by tdTomato electroporated neuroblasts in the RMS. However, microglia wrap DsRed-labeled neuroblasts in the RMS of P7 CX3CR-1GFP/+;DCXDsRed/+ mice and express the phagocytic markers CD68, CLEC7A and MERTK, suggesting active phagocytosis of neuroblasts in the developing RMS. Microglia depletion for 14 days postnatally further induced an accumulation of DCX+ neuroblasts and CC3+ apoptotic cells 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 phagocytosis in maintaining the homeostasis of the early postnatal RMS.SIGNIFICANCE STATEMENTMicroglia are brain-resident immune cells responsible for both maintaining homeostatic conditions necessary for normal neurodevelopment as well as orchestrating the brain’s response to environmental insults. The effects of microglia-mediated immune response during development may be of special relevance to the olfactory system, which is unique in both its vulnerability to environmental insults as well as its extended period of neurogenesis and neuronal migration. The work presented here 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 microglia phagocytosis in the early postnatal RMS and provides insights into microglia function during periods of neurogenesis and neuronal migration.