Microglia: Brain cells on the move

In the last decade, tremendous progress has been made in understanding the biology of microglia – i.e. the fascinating immigrated resident immune cell population of the central nervous system (CNS). Recent literature reviews have largely dealt with the plentiful functions of microglia in CNS homeostasis, development and pathology, and the influences of sex and the microbiome. In this review, the intriguing aspect of their physical plasticity during CNS development will get specific attention. Microglia move around (mobility) and reshape their processes (motility). Microglial migration into and inside the CNS is most prominent throughout development and consequently most of the data described in this review concern mobility and motility in the changing environment of the developing brain. Here, we first define microglia based on their highly specialized age- and region-dependent gene expression signature and associated functional heterogeneity. Next, we describe their origin, the migration route of immature microglial cells towards the CNS, the mechanisms underlying their invasion 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 microenvironment of the CNS. Therefore, we further zoom in on the changing environment during CNS development. We elaborate on the extracellular matrix and the respective integrin receptors on microglia and we discuss the purinergic and molecular signalling in microglial mobility. In the last section, we discuss the physiological and pathological functions of microglia in which mobility and motility are involved to stress the importance of microglial ‘movement’.