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CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development

Emily K Lehrman1, Daniel K Wilton1, Elizabeth Y Litvina1

  • 1Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Neuron
|October 12, 2018
PubMed

Insights

CD47-SIRPα signaling acts as a brake on microglia, preventing inappropriate synapse removal during brain development. This innate immune pathway protects synapses from excessive engulfment by microglia.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Microglia are crucial for synaptic remodeling and phagocytosis in the healthy brain.
  • Mechanisms governing selective synapse engulfment by microglia are not fully understood.

Purpose of the Study:

  • To investigate the role of innate immune signaling in regulating microglial synapse pruning.
  • To identify molecular mechanisms that prevent inappropriate microglial phagocytosis of synapses.

Main Methods:

  • Analysis of CD47 and SIRPα expression patterns during retinogeniculate system development.
  • Utilized CD47-deficient mice to assess microglial engulfment and synapse numbers.
  • Electrophysiological recordings to measure functional synaptic pruning.
  • Investigated activity-dependent engulfment in CD47 knockout mice.

Main Results:

  • CD47 and SIRPα expression correlated with peak synaptic pruning.
  • Mice lacking CD47 showed increased microglial engulfment and reduced synapse numbers.
  • CD47 deficiency led to enhanced functional pruning and impaired activity-dependent engulfment.

Conclusions:

  • CD47-SIRPα signaling acts as a critical brake, preventing excessive microglial phagocytosis of synapses.
  • This pathway is essential for protecting specific neuronal inputs from inappropriate removal.
  • Activity-dependent regulation of synaptic pruning is mediated by CD47 signaling.
Keywords:
CD47SIRPαactivitydon’t eat memicrogliaphagocytosisprotective signalpruningrefinementretinogeniculate system

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