Abstract
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, contributing to both innate and adaptive immune responses locally, 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. While microglia have been studied for decades, a long history of experimental misinterpretation meant that their true origins remained debated. However, recent studies on microglial origin indicate that these cells in fact arise early during development from progenitors in the embryonic yolk sac (YS) that seed the brain rudiment and, remarkably, appear to persist there into adulthood. Here, we review the history of microglial cells and discuss the latest advances in our understanding of their origin, differentiation, and homeostasis, which provides new insights into their roles in health and disease.
Highlights
Microglia are the resident mononuclear phagocytes of the central nervous system (CNS), belonging to the glial system of non-neuronal cells that support and protect neuronal functions
In 1993, Lassmann and co-workers were the first to demonstrate that resident microglia in rats are a very stable cell pool, in contrast to meningeal and perivascular macrophages, which in adult animals are only exceptionally replaced by circulating blood cells, even after recovery from severe brain inflammation (Lassmann et al, 1993)
We have learned that microglia arise from yolk sac (YS) macrophages that seed the brain rudiment from the cephalic mesenchyme very early during development, as predicted earlier by the founder of the microglia field, Pio del Rio-Hortega
Summary
Florent Ginhoux1*, Shawn Lim 2, Guillaume Hoeffel, Donovan Low 1 and Tara Huber 2,3. Adequate microglial function is crucial for a healthy CNS. 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. While microglia have been studied for decades, a long history of experimental misinterpretation meant that their true origins remained debated. Recent studies on microglial origin indicate that these cells arise early during development from progenitors in the embryonic yolk sac (YS) that seed the brain rudiment and, remarkably, appear to persist there into adulthood. We review the history of microglial cells and discuss the latest advances in our understanding of their origin, differentiation, and homeostasis, which provides new insights into their roles in health and disease
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