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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Embryonic microglia maintain the brain's cortical fault lines

Anushree S Gupte1, T Yvanka de Soysa1, Beth Stevens2

  • 1Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Trends in Immunology
|April 25, 2024
PubMed

Insights

Fetal brain development involves microglia responding to stress at cortical boundaries. These cells prevent lesion formation by clearing fibronectin, a key finding for understanding brain development and injury.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Immunology

Background:

  • Fetal cortical development involves complex cellular interactions.
  • Microglia, the brain's immune cells, play critical roles beyond immune surveillance.
  • The specific functions of microglia at fetal cortical boundaries are not well understood.

Purpose of the Study:

  • To investigate the role of microglia at fetal cortical boundaries.
  • To understand how morphogenetic stress influences microglia states.
  • To identify the mechanisms by which microglia prevent cavitary lesion formation.

Main Methods:

  • Analysis of microglia states in response to fetal cortical stress.
  • Investigation of the molecular regulation of microglia function, including Spp1.
  • Assessment of phagocytosis of extracellular matrix proteins like fibronectin 1.

Main Results:

  • Fetal cortical boundaries are sensitive to morphogenetic stress.
  • This stress induces a microglia state similar to postnatal axon-tract associated microglia (ATM).
  • This ATM-like state prevents cavitary lesion formation via Spp1-regulated fibronectin 1 phagocytosis.

Conclusions:

  • Microglia exhibit a specialized, protective function at fetal cortical boundaries.
  • The Spp1-mediated phagocytosis pathway is crucial for preventing lesions during development.
  • These findings reveal a novel role for microglia in maintaining brain structural integrity during development.

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