Microglia in the CNS: Immigrants from Another World

Microglia are immunocompetent cells of the brain that continuously survey their environment with highly motile extensions. Although first described almost a century ago, the developmental origin of microglia is still debated. Besides early myeolomonocytic cell populations that colonize the developing neuroectoderm already during embryogenesis, newly migrated myeloid cells are considered important disease modulators in the adult brain. Thus, understanding the mechanisms of myeloid cell recruitment from the periphery and their development into bone marrow-derived phagocytes in the adult brain is pivotal for manipulating immune cell entry into the CNS and potentially reducing disease burden. A major question is whether bone marrow-derived mononuclear phagocytes have similar features and fates as their endogenous counterparts. Significant advances in our understanding of microglia biology under physiological as well as under pathological conditions have been made in the last few years, especially by combining novel gene-targeting techniques that allow cell manipulation and trafficking analysis. These new aspects will be discussed in the present review.