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Vault immunofluorescence in the brain: new insights regarding the origin of microglia
D C Chugani1, N L Kedersha, L H Rome
1Department of Radiological Sciences, UCLA School of Medicine 90024.
Abstract:
The developmental appearance of ameboid and ramified microglia in the rat brain has been examined by immunofluorescent localization of vaults, recently described ribonucleoprotein particles (Kedersha and Rome, 1986a). Vaults are distinct, multiarched structures of unknown function expressed by higher and lower eukaryotic species. Although vaults have been detected in all mammalian cells examined to date, they are highly enriched in macrophages. In the brain, vault antisera is highly specific for both ameboid and ramified microglia. The developmental profile of vault immunoreactivity in rat brain slices suggests that microglia enter the brain at 2 locations, with different time scales for each. The first migration, which begins before embryonic day 15 and subsides between postnatal days 7 and 14, was identified by vault immunoreactivity and Bandeiraea simplicifolia B4-isolectin (a microglia marker) staining. The cells appear to enter from blood vessels and display a ramified morphology as soon as they are detected in the brain. The second microglial migration occurs in the first postnatal week, when ameboid microglia appear in the corpus callosum and other large fiber tracts. Ameboid microglia appear to differentiate into ramified microglia between postnatal days 4 and 14. Vault immunoreactivity, as a very early microglial marker, provides new insight regarding the much-debated origin of the ramified microglia. It is quite clear that ameboid cells are not the sole source of ramified microglia because ramified cells can be detected before the influx of ameboid microglia. Colocalization studies with monocyte/macrophage markers ED1 and OX42 demonstrate that both ramified and ameboid microglia originate from monocyte lineage.
Insights
Vaults, a novel marker, reveal two distinct microglial migration routes into the developing rat brain. This study clarifies microglial origins, showing both ameboid and ramified forms arise from monocytes.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's resident immune cells, exist in ameboid and ramified forms.
- Their developmental origins and migration patterns in the rat brain are not fully understood.
- Vaults are ribonucleoprotein particles found in various species, highly expressed in macrophages.
Purpose of the Study:
- To investigate the developmental appearance and origin of ameboid and ramified microglia in the rat brain.
- To utilize vault immunofluorescence as a specific marker for microglia.
- To elucidate the migration routes and differentiation of microglia during brain development.
Main Methods:
- Immunofluorescent localization of vaults in developing rat brain slices.
- Staining with Bandeiraea simplicifolia B4-isolectin and monocyte/macrophage markers (ED1, OX42).
- Analysis of microglial morphology and distribution across different developmental stages.
Main Results:
- Vaults are highly specific markers for both ameboid and ramified microglia in the rat brain.
- Two distinct microglial migration events were identified: one prenatal/early postnatal via blood vessels, and a second postnatal influx.
- Ramified microglia appear early, predating the main influx of ameboid microglia, and both cell types originate from the monocyte lineage.
Conclusions:
- Vault immunoreactivity provides a novel and early marker for tracking microglial development.
- Microglia enter the brain through at least two distinct migratory pathways.
- Both ameboid and ramified microglia are derived from circulating monocytes, challenging previous assumptions about their sole origins.