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Updated: May 12, 2026
Isolation of Mouse Primary Microglia by Magnetic-Activated Cell Sorting in Animal Models of Demyelination
Published on: April 5, 2022
Origin and differentiation of microglia
Florent Ginhoux1, Shawn Lim, Guillaume Hoeffel
1Singapore Immunology Network, Agency for Science, Technology, and Research Singapore.
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.
Insights
Microglia, the central nervous system (CNS) immune cells, originate from embryonic yolk sac progenitors and are vital for brain health and homeostasis. Their roles in neuronal development and synaptic formation are increasingly recognized.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are the primary immune cells residing in the central nervous system (CNS).
- Their functions extend beyond immune surveillance to include maintaining brain homeostasis and regulating neuronal development.
- Historically, the precise origin of microglia has been a subject of debate due to experimental challenges.
Purpose of the Study:
- To review the historical understanding of microglia.
- To discuss recent advancements in understanding microglial origin, differentiation, and homeostasis.
- To highlight the multifaceted roles of microglia in CNS health and disease.
Main Methods:
- Review of historical literature on microglia.
- Analysis of recent developmental biology studies on microglial origins.
- Synthesis of current research on microglial function and homeostasis.
Main Results:
- Microglia originate from embryonic yolk sac progenitors.
- These progenitors migrate to the brain during early development and persist into adulthood.
- Microglia play fundamental roles in neuronal proliferation, differentiation, and synapse formation.
Conclusions:
- The embryonic yolk sac origin of microglia is now well-established.
- Understanding microglial development and homeostasis offers new therapeutic targets for neurological diseases.
- Microglia are critical regulators of CNS function throughout life.
