Microglial trogocytosis and the complement system regulate axonal pruning in vivo

• Published in: eLife Vol. 10
• Main Authors: Lim, Tony Ky, Ruthazer, Edward S
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 16-03-2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Amphibians; axon; Axons; behavior; Bioinformatics; CD46 antigen; Complement activation; Complement component C3; Fusion protein; Hypotheses; Immunology and Inflammation; Kinases; Lasers; Membrane fusion; Microglia; Morphology; morphometry; Neural circuitry; Neuroscience; Phagocytosis; Plasma membranes; Protein binding; Proteins; pruning; Retina; retinotectal; Superior colliculus; pruning; retinotectal; inflammation; neuroscience; xenopus; morphometry; axon; behavior; immunology; microglia
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.62167

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
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.