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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

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Type-I-interferon-responsive microglia shape cortical development and behavior

Caroline C Escoubas1, Leah C Dorman2, Phi T Nguyen3

  • 1Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Cell
|March 15, 2024
PubMed

Insights

Type I interferons (IFN-I) activate microglia to engulf neurons during brain development. Loss of IFN-I signaling impairs this process, leading to excess neurons and sensory hypersensitivity.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Microglia, the brain's immune cells, play crucial roles in neural development and are linked to neurodevelopmental disorders.
  • While distinct microglial states exist, their functional roles remain largely unknown.

Purpose of the Study:

  • To identify and characterize a specific microglial state involved in neural circuit development.
  • To elucidate the functional significance of type I interferon (IFN-I) signaling in microglial activity and brain development.

Main Methods:

  • Transcriptional profiling of microglia in the developing somatosensory cortex.
  • Investigating microglial engulfment of neurons using in vivo models (mouse and zebrafish).
  • Utilizing genetic manipulation (loss and gain of IFN-I receptor function) and experimental stimuli (whisker deprivation).

Main Results:

  • Identified a type I interferon (IFN-I)-responsive microglial population actively engulfing neurons in the developing cortex.
  • IFN-I receptor deficiency led to microglial phagolysosomal dysfunction and accumulation of DNA-damaged neurons.
  • IFN-I gain of function enhanced neuronal engulfment and reduced DNA-damaged neurons.
  • IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity.

Conclusions:

  • Neuron-engulfing microglia, regulated by IFN-I signaling, play a critical role during a key window of brain development.
  • Canonical antiviral IFN-I pathways exert homeostatic functions within the developing brain, influencing neuronal populations and sensory processing.
Keywords:
cortical developmentmicroglianeuroimmunityphagocytosissomatosensory cortextactile hypersensitivitytype I interferon

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