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

Microglia are the immune effector cells of the nervous system. The prevaili ng view is that microglia are derived from circulating precursors in the bl ood, which originate from the bone-marrow. Colonisation of the central nerv ous system (CNS) by microglia is an orchestrated response during human feta l development related to the maturation of the nervous system. It coincides with vascularisation, formation of radial glia, neuronal migration and mye lination primarily in the 4th-5th months and beyond. Microglial influx gene rally conforms to a route following white matter tracts to gray areas. We h ave observed that colonisation of the spinal cord begins around 9 weeks, wi th the major influx and distribution of microglia commencing around 16 week s. In the cerebrum, colonisation is in progress during the second trimester , and ramified microglial forms are widely distributed within the intermedi ate 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 vasc ulature. The distribution of these cells is likely to be co-ordinated by sp atially and temporally regulated, anatomical expression of chemokines inclu ding RANTES and MCP-I in the cortex; by ICAM-2 and PECAM on radiating cereb ral vessels and on capillaries within the germinal layer, and apoptotic cel l 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 c ontribute towards CNS histogenesis. (C) 1999 Wiley-Liss,Inc.