Abstract
Microglia are unique brain-resident, myeloid cells. They have received growing interest for their implication in an increasing number of neurodevelopmental, acute injury, and neurodegenerative disorders of the central nervous system (CNS). Fate-mapping studies establish microglial ontogeny from the periphery during development, while recent transcriptomic studies highlight microglial identity as distinct from other CNS cells and peripheral myeloid cells. This evidence for a unique microglial ontogeny and identity raises questions regarding their identity and functions across species. This review will examine the available evidence for microglia in invertebrate and vertebrate species to clarify similarities and differences in microglial identity, ontogeny, and physiology across species. This discussion highlights conserved and divergent microglial properties through evolution. Finally, we suggest several interesting research directions from an evolutionary perspective to adequately understand the significance of microglia emergence. A proper appreciation of microglia from this perspective could inform the development of specific therapies geared at targeting microglia in various pathologies.