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.
Keywords: axon; behavior; immunology; inflammation; microglia; morphometry; neuroscience;
pruning; retinotectal; xenopus.
Reference
Lim, T. K., & Ruthazer, E. S. (2021). Microglial trogocytosis and the complement system regulate axonal pruning in vivo. Elife, 10, e62167.