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Elife 2021 Mar 16;10. doi: 10.7554/eLife.62167.
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Microglial trogocytosis and the complement system regulate axonal pruning in vivo.

Lim TK , Ruthazer ES .

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.

PubMed ID: 33724186
PMC ID: PMC7963485
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: c3 csf1r polr2a prune1 syp vamp2
GO keywords: phagocytosis [+]

Article Images: [+] show captions
References [+] :
Agarwala, Database resources of the National Center for Biotechnology Information. 2019, Pubmed