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Updated: Aug 11, 2025
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
CD206+ macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia
Yuki Hattori1, Daisuke Kato2, Futoshi Murayama1
1Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Abstract:
The relationships between tissue-resident microglia and early macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding in situ and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated or genetic labeling, we find that intraventricular CD206+ macrophages, which are abundantly observed along the inner surface of the mouse cerebral wall, frequently enter the pallium at embryonic day 12. Immunofluorescence of the tracked cells show that postinfiltrative macrophages in the pallium acquire microglial properties while losing the CD206+ macrophage phenotype. We also find that intraventricular macrophages are supplied transepithelially from the roof plate. This study demonstrates that the "roof plate→ventricle→pallium" route is an essential path for microglial colonization into the embryonic mouse brain.
Insights
Newly identified macrophages colonize the embryonic mouse brain, converting into microglia. This study reveals the "roof plate→ventricle→pallium" route as a key pathway for brain microglial seeding.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia are crucial for brain development and function.
- Their origin and seeding mechanisms in the embryonic brain remain incompletely understood.
- Previous models suggest macrophage conversion to microglia, but in situ evidence is lacking.
Purpose of the Study:
- To investigate the spatiotemporal dynamics of microglial seeding in the embryonic mouse brain.
- To identify the origin and migratory route of cells that give rise to microglia.
- To provide in situ evidence for macrophage-to-microglia conversion during brain development.
Main Methods:
- Cell tracking using slice culture and intravital imaging.
- Flash tag-mediated and genetic labeling techniques.
- Immunofluorescence to analyze cell phenotype changes.
Main Results:
- Intraventricular CD206+ macrophages were observed entering the pallium at embryonic day 12.
- Post-infiltrative cells acquired microglial properties while losing their macrophage phenotype.
- Intraventricular macrophages originate from the roof plate via transepithelial supply.
Conclusions:
- The study demonstrates a novel "roof plate→ventricle→pallium" route for microglial colonization.
- This pathway is essential for seeding microglia in the developing mouse brain.
- Macrophage-to-microglia conversion occurs in situ within the embryonic brain parenchyma.
