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Microglia across evolution: from conserved origins to functional divergence.

Takashi Shimizu1, Marco Prinz2,3,4

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|November 22, 2025
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Microglia, the brain's immune cells, share core features across species but vary in form and function due to evolution. Understanding these differences is key for developing new neurological disorder treatments.

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Area of Science:

  • Neuroimmunology
  • Evolutionary biology
  • Cellular biology

Background:

  • Microglia are the central nervous system (CNS) resident immune cells.
  • They have conserved developmental origins and molecular signatures across vertebrates.
  • Homeostatic functions like immune surveillance and synaptic pruning are conserved, but morphology and responses vary evolutionarily.

Purpose of the Study:

  • To review conserved and divergent aspects of microglial biology across vertebrate evolution.
  • To integrate findings from various model organisms (zebrafish, rodents, nonhuman primates) and humans.
  • To highlight the importance of evolutionary differences for translating research and developing therapies.

Main Methods:

  • Literature review integrating findings from diverse vertebrate species.
  • Comparative analysis of microglial morphology, gene expression, and functional responses.
  • Examination of evolutionary factors influencing microglial divergence.

Main Results:

  • Microglia display conserved core functions and molecular signatures across vertebrate phylogeny.
  • Significant species-specific variations exist in microglial morphology, gene expression, and stimulus response.
  • Evolutionary divergence is shaped by factors including lifespan, regenerative capacity, and immune system architecture.

Conclusions:

  • Understanding evolutionary divergence in microglia is crucial for cross-species research translation.
  • Comparative microglial biology provides insights into species-specific adaptations.
  • Integrating evolutionary perspectives is vital for advancing microglia-targeted therapies for neurological disorders.