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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Colonisation of the developing human brain and spinal cord by microglia: a review
1Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom. p.rezaie@iop.kcl.ac.uk
Abstract:
Microglia are the immune effector cells of the nervous system. The prevailing view is that microglia are derived from circulating precursors in the blood, which originate from the bone-marrow. Colonisation of the central nervous system (CNS) by microglia is an orchestrated response during human fetal development related to the maturation of the nervous system. It coincides with vascularisation, formation of radial glia, neuronal migration and myelination primarily in the 4th-5th months and beyond. Microglial influx generally conforms to a route following white matter tracts to gray areas. We have observed that colonisation of the spinal cord begins around 9 weeks, with the major influx and distribution of microglia commencing around 16 weeks. In the cerebrum, colonisation is in progress during the second trimester, and ramified microglial forms are widely distributed within the intermediate zone by the first half of intra-uterine life (20-22 weeks). A distinct pattern of migration occurs along radial glia, white matter tracts and vasculature. The distribution of these cells is likely to be co-ordinated by spatially and temporally regulated, anatomical expression of chemokines including RANTES and MCP-1 in the cortex; by ICAM-2 and PECAM on radiating cerebral vessels and on capillaries within the germinal layer, and apoptotic cell death overlying this region. The phenotype and functional characteristics of fetal microglia are also outlined in this review. The need for specific cellular interactions and targeting is greater within the central nervous system than in other tissues. In this respect, microglia may additionally contribute towards CNS histogenesis.
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.

