The molecular determinants of microglial developmental dynamics

Microglia constitute the largest population of parenchymal macrophages in the brain and are considered a unique subset of central nervous system glial cells owing to their extra-embryonic origins in the yolk sac. During development, microglial progenitors readily proliferate and eventually colonize the entire brain. In this Review, we highlight the origins of microglial progenitors and their entry routes into the brain and discuss the various molecular and non-molecular determinants of their fate, which may inform their specific functions. Specifically, we explore recently identified mechanisms that regulate microglial colonization of the brain, including the availability of space, and describe how the expansion of highly proliferative microglial progenitors facilitates the occupation of the microglial niche. Finally, we shed light on the factors involved in establishing microglial identity in the brain. The developmental colonization of the brain by microglial progenitors and establishment of microglial cell identity set the stage for microglial function in the adult. Barry-Carroll and Gomez-Nicola describe the mechanisms that regulate the development of microglia, including their origins, infiltration and colonization of the brain, proliferation and fate determination.