Microglia: Brain cells on the move

Abstract

In the last decade, tremendous progress has been made in understanding the biology of microglia – i.e. thefascinating immigrated resident immune cell population of the central nervous system (CNS). Recent literaturereviews have largely dealt with the plentiful functions of microglia in CNS homeostasis, development and pa-thology, and the influences of sex and the microbiome. In this review, the intriguing aspect of their physicalplasticity during CNS development will get specific attention. Microglia move around (mobility) and reshapetheir processes (motility). Microglial migration into and inside the CNS is most prominent throughout devel-opment and consequently most of the data described in this review concern mobility and motility in thechangingenvironmentofthedevelopingbrain.Here,wefirstdefinemicrogliabasedontheirhighlyspecializedage-andregion-dependentgeneexpressionsignatureandassociatedfunctionalheterogeneity.Next,wedescribetheirorigin,themigrationrouteofimmaturemicroglialcellstowardstheCNS,themechanismsunderlyingtheirinvasion of the CNS, and their spatiotemporal localization and surveying behaviour inside the developing CNS.These processes are dependent on microglial mobility and motility which are determined by the micro-environmentoftheCNS.Therefore,wefurtherzoominonthechangingenvironmentduringCNSdevelopment.We elaborate on the extracellular matrix and the respective integrin receptors on microglia and we discuss thepurinergic and molecular signalling in microglial mobility. In the last section, we discuss the physiological andpathological functions of microglia in which mobility and motility are involved to stress the importance ofmicroglial ‘movement’