Origin of microglia
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Updated: Aug 18, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
1Department of Anatomy, Faculty of Medicine, National University of Singapore, Singapore.
Abstract:
This paper reviews the various proposed hypotheses on the origin of microglia. The seminal study of del Rio-Hortega first stated that the cells were derived from the mesodermal pial cells that invaded the brain during embryonic development. Along with this was the description of precursor cells in the yolk sac in early development. Our results in the embryonic mouse brain have shown the occurrence of lectin-labelled precursor cells at the yolk sac that later appeared in the mesenchymal tissue associated with the neuroepithelium where they penetrated the nervous tissue to become the microglia. A second major view has held that microglia are of neuroectodermal origin; the cells either originate from glioblasts or the germinal matrix. Another school of thought is that microglia are derived from blood monocytes. In this connection, circulating monocytes enter the developing brain to assume the form as amoeboid microglia that subsequently evolve to become the ramified microglia. In traumatic brain lesions following an intravenous injection of colloidal carbon as a cytoplasmic marker for monocytes, it was found that carbon-labelled monocytes were the main source of brain macrophages, some of which transformed into microglia during the healing process. In conclusion, our results derived from the normal and altered brain development as well as from experimental lesions tend to favour the view of the monocytic nature of microglia. Recent studies by us also point to the possibility that some microglial cells may arise from the pial mesenchymal macrophages that appear to originate from the yolk sac precursors.
Insights
Microglia, crucial brain immune cells, originate from yolk sac precursors. Research suggests these cells migrate to the brain, supporting a monocytic origin for microglia.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- The origin of microglia, the resident immune cells of the central nervous system, has been a long-standing debate in neuroscience.
- Historically, hypotheses have proposed origins from neuroectodermal cells, pial cells, or circulating blood monocytes.
Purpose of the Study:
- To review existing hypotheses on microglial origins.
- To present experimental evidence from embryonic mouse brains and experimental brain lesions to elucidate microglial cell lineage.
Main Methods:
- Tracing lectin-labelled precursor cells in embryonic mouse brains originating from the yolk sac.
- Utilizing colloidal carbon injection in traumatic brain lesions to label circulating monocytes.
- Observing the transformation of monocytes into microglia during the healing process.
Main Results:
- Lectin-labelled precursor cells were identified in the yolk sac, migrating to the brain's mesenchymal tissue and differentiating into microglia.
- In experimentally induced brain lesions, carbon-labelled monocytes were the primary source of brain macrophages, some transforming into microglia.
- Findings support the monocytic origin of microglia, with potential contributions from pial mesenchymal macrophages derived from yolk sac precursors.
Conclusions:
- The study's findings favor the monocytic origin of microglia based on evidence from normal and altered brain development and experimental lesions.
- A dual origin is suggested, with microglia potentially arising from both circulating monocytes and pial mesenchymal macrophages originating from yolk sac precursors.
