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A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
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Microglial trogocytosis and the complement system regulate axonal pruning in vivo.

Tony Ky Lim1, Edward S Ruthazer1

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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.

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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.