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Updated: Oct 14, 2026
An Engulfment Assay: A Protocol to Assess Interactions Between CNS Phagocytes and Neurons
Published on: June 8, 2014
Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the
Vivianne Morrison1, Matthew Houpert2, Jonathan Trapani2
1Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA; Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Abstract:
Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to 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 a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1β signaling; interleukin-1 receptor inhibition rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ.
Insights
Microglia in the brain
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are key immune cells in the central nervous system (CNS).
- Their phagocytic activity influences the CNS environment and cell phenotypes.
- The role of microglia in the neonatal ventricular-subventricular zone (V-SVZ) neurogenic niche is unclear.
Purpose of the Study:
- To investigate the role of microglial phagocytosis in the developing V-SVZ.
- To identify the mechanisms by which microglia influence neural precursor cells.
Main Methods:
- Utilized mouse models to study microglia in the V-SVZ.
- Investigated the function of the engulfment receptor Jedi-1 in microglial phagocytosis.
- Analyzed the impact of phagocytosis on neural precursor proliferation and microglial phenotype.
Main Results:
- Phagocytosis by V-SVZ microglia promotes a pro-neurogenic phenotype.
- The engulfment receptor Jedi-1 mediates apoptotic cell clearance by these microglia.
- Deletion of Jedi-1 impairs phagocytosis, leading to a neuroinflammatory phenotype.
- This inflammation reduces neural precursor proliferation via interleukin-1β signaling.
Conclusions:
- Jedi-1 is crucial for microglial phagocytosis in the V-SVZ.
- Microglial phagocytic activity is essential for maintaining a pro-neurogenic niche.
- Dysfunctional phagocytosis contributes to neuroinflammation and reduced neurogenesis.
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