Microglia are the resident macrophages of the central nervous system (CNS) 1. Expanding on previous developmental studies 2,3, recent genetic lineage tracing in the mouse determined that microglia take up residence in the developing neural tube shortly before closure of the blood-brain barrier 4. They emigrate as erythromyeloid precursors or primitive macrophages from the yolk sac, before further hematopoiesis takes place in the periphery. In contrast to other adult tissue monocyte-derived macrophages, microglial identity is a combination of unique mesodermal ontogeny (primitive myelopoiesis) and lifelong residence in an immune-privileged neuro-glial environment. Their phenotype is shaped by the developmental stages of the nervous system as it transitions from neurogenesis and gliogenesis, to synaptogenesis and network maturation 5, to a largely post-mitotic aging tissue in absence of injury.
