Colonisation of the developing human brain and spinal cord by microglia: a review

P Rezaie1, D Male

  • 1Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom. p.rezaie@iop.kcl.ac.uk

Insights

Microglia, the brain's immune cells, originate from bone marrow precursors. Their colonization of the developing central nervous system (CNS) follows specific pathways and timing during fetal development.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Microglia are the primary immune cells of the central nervous system (CNS).
  • The prevailing theory posits that microglia originate from bone marrow-derived circulating precursors.
  • Their colonization of the CNS is a crucial, orchestrated process during human fetal development.

Purpose of the Study:

  • To review the developmental origin and colonization patterns of microglia within the human fetal CNS.
  • To elucidate the timing, routes, and regulatory mechanisms of microglial migration.
  • To outline the phenotype and functional characteristics of fetal microglia.

Main Methods:

  • Review of existing literature on microglial development and CNS colonization.
  • Analysis of temporal and spatial patterns of microglial distribution during human fetal development.
  • Examination of molecular cues (chemokines, adhesion molecules) and cellular interactions guiding migration.

Main Results:

  • Microglial colonization of the CNS is linked to nervous system maturation, vascularization, and neuronal development.
  • Specific timing observed: spinal cord colonization begins around 9 weeks, major influx around 16 weeks; cerebral colonization occurs during the second trimester.
  • Migration follows white matter tracts, radial glia, and vasculature, guided by chemokines (RANTES, MCP-1) and adhesion molecules (ICAM-2, PECAM).

Conclusions:

  • Fetal microglia exhibit distinct migration patterns and distribution within the developing CNS.
  • Their colonization is a precisely regulated process involving molecular signaling and anatomical cues.
  • Microglia may play a role beyond immune surveillance, potentially contributing to CNS histogenesis.

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