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Published on: April 13, 2017
Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the
Vivianne E Morrison1,2,3, Matthew G Houpert1,2, Jonathan B Trapani1,2
1Vanderbilt University Department of Biochemistry.
Abstract:
Microglia are the primary phagocytes in the central nervous system and are responsible for clearing dead cells generated during development or disease. The phagocytic process shapes the phenotype of the microglia, which affects the local environment. A unique population of microglia reside in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence this neurogenic niche is not well-understood. Here, we demonstrate that phagocytosis creates a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering the development of a neuroinflammatory phenotype, reminiscent of neurodegenerative and-age-associated microglia, that reduces neural precursor proliferation via elevated interleukin (IL)-1β signaling; inhibition of IL-1 receptor rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to a phenotype that promotes neurogenesis in the developing V-SVZ.
Insights
Microglia phagocytosis in the developing brain promotes neurogenesis. Deleting Jedi-1 impairs this process, leading to inflammation and reduced neural precursor proliferation.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are central nervous system immune cells crucial for clearing cellular debris.
- The ventricular-subventricular zone (V-SVZ) is a key neurogenic niche in neonatal mice.
- The specific role of microglia in the V-SVZ neurogenic niche remains unclear.
Approach:
- Investigated the role of microglial phagocytosis in the V-SVZ of neonatal mice.
- Utilized genetic deletion of the engulfment receptor Jedi-1 to study its function.
- Analyzed the impact on microglial phenotype, apoptotic cell clearance, and neural precursor proliferation.
Key Points:
- Phagocytosis by V-SVZ microglia induces a pro-neurogenic phenotype.
- The engulfment receptor Jedi-1 mediates apoptotic cell clearance by these microglia.
- Jedi-1 deletion results in reduced phagocytosis, a neuroinflammatory phenotype, and decreased neural precursor proliferation.
- Elevated interleukin-1 beta (IL-1β) signaling mediates the inhibitory effect on precursor proliferation.
Conclusions:
- Jedi-1 is critical for maintaining a neurogenic microglial phenotype in the V-SVZ.
- Microglial phagocytic activity, mediated by Jedi-1, is essential for regulating neurogenesis in the developing brain.
- Targeting Jedi-1 or IL-1β signaling may offer therapeutic avenues for neurodevelopmental or neurodegenerative conditions.
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