Figure 1.

Brain development and microglial homeostasis. Primitive macrophages exit the yolk sac blood islands at the onset of circulation and colonize the neuroepithelium from E9.5 to give rise to microglia. The blood brain barrier starts to form from E13.5 and may isolate the developing brain from the contribution of fetal liver hematopoiesis. Embryonic microglia expand and colonize the whole CNS until adulthood. Importantly, in steady state conditions, embryonically-derived microglia will maintain themselves until adulthood, via local proliferation during late gestation and post-natal development as well as in the injured adult brain in reaction to inflammation. Nevertheless, during certain inflammatory conditions found for example after bone marrow transplantation, the recruitment of monocytes or other bone marrow-derived progenitors can supplement the microglial population to some extent. However, we do not understand yet whether these cells persist and become integrated in the microglial network, or are a temporary addition to the endogenous population.