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Updated: Nov 12, 2025
A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
Microglial trogocytosis and the complement system regulate axonal pruning in vivo
Tony Ky Lim1, Edward S Ruthazer1
1Department of Neurology & Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Canada.
Abstract:
Partial phagocytosis-called trogocytosis-of axons by microglia has been documented in ex vivo preparations but has not been directly observed in vivo. The mechanisms that modulate microglial trogocytosis of axons and its function in neural circuit development remain poorly understood. Here, we directly observe axon trogocytosis by microglia in vivo in the developing Xenopus laevis retinotectal circuit. We show that microglia regulate pruning of retinal ganglion cell axons and are important for proper behavioral response to dark and bright looming stimuli. Using bioinformatics, we identify amphibian regulator of complement activation 3, a homolog of human CD46, as a neuronally expressed synapse-associated complement inhibitory molecule that inhibits trogocytosis and axonal pruning. Using a membrane-bound complement C3 fusion protein, we demonstrate that enhancing complement activity enhances axonal pruning. Our results support the model that microglia remodel axons via trogocytosis and that neurons can control this process through expression of complement inhibitory proteins.
Insights
Microglia partially engulf axons (trogocytosis) in vivo, regulating neural circuit development and behavior. Neurons control this process via complement inhibitory proteins like regulator of complement activation 3.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglial partial phagocytosis of axons (trogocytosis) is known ex vivo but unobserved in vivo.
- Mechanisms and functions of microglial trogocytosis in neural development are poorly understood.
Purpose of the Study:
- To directly observe and characterize microglial axon trogocytosis in vivo.
- To elucidate the mechanisms and functional significance of this process in neural circuit development.
Main Methods:
- Direct in vivo observation of microglial axon trogocytosis in the developing Xenopus laevis retinotectal circuit.
- Bioinformatic analysis to identify regulatory molecules.
- Experimental manipulation of complement activity.
Main Results:
- Directly observed microglial trogocytosis of axons in vivo.
- Demonstrated that microglia regulate retinal ganglion cell axon pruning and influence behavioral responses.
- Identified amphibian regulator of complement activation 3 (a CD46 homolog) as a neuronal complement inhibitor of trogocytosis.
- Showed that enhanced complement activity increases axonal pruning.
Conclusions:
- Microglia remodel axons through trogocytosis in vivo.
- Neurons regulate microglial axon remodeling via complement inhibitory proteins.
