Microglial ontogeny and functions in shaping brain circuits

Microglia are the resident macrophage population of the central nervous system (CNS). Adequate microglial function is crucial for a healthy CNS; microglia are not only the first immune sentinels of infection and inflammation, but are also involved in the maintenance of brain homeostasis. Emerging data are showing new and fundamental roles for microglia in the control of neuronal proliferation and differentiation, as well as in the formation of synaptic connections. In parallel, recent studies on microglial origin indicate that these cells arise very early during development from progenitors in the embryonic yolk sac that produce cells able to persist in the CNS into adulthood. These unique immune cells are thus present at all stages of brain development, including the prenatal stage of neuronal circuit formation, which points to the intriguing possibility that microglia might be involved in development of the CNS. Here, we review the latest advances in our understanding of the origin, differentiation, and homeostasis of microglial cells. In light of this knowledge, we then discuss the microglial contribution to CNS development and their emerging significance in the field of CNS disease.