Microglia in the Human Nervous System during Development

Abstract

Microglia are the principal resident mononuclear phagocytes of the central nervous system (CNS). They are representatives of the immune system intrinsic to this organ. These cells are morphologically, phenotypically and functionally distinct from other populations of mononuclear phagocytes associated with the CNS, such as perivascular macrophages, supraependymal macrophages, epiplexus cells of the choroid plexus and meningeal macrophages. While the origin of microglia has been the subject of controversy for many years, the prevailing view holds that they are derived from mesenchyme (mesodermal elements) or from circulating blood mononuclear progenitors (monocytes) that penetrate the nervous tissues early in development. This article will review the location, distribution, morphology and phenotype of microglia in the developing human CNS. Potential functional roles for microglia are discussed in relation to developmental events.

The Yin and Yang of Microglia

“…Amoeboid microglia constitute specific clusters after they have penetrated the parenchyma [30]. These specific clusters at the junctions of the internal capsule with the thalamus, with the external capsule and with the cerebral peduncle, as well as at the junctions of the cerebral peduncle with the optic tract, the medial septum, the periventricular hypothalamic area and the corpus callosum, are transient in the developing brain [30]. In the cortical layers and white matter, microglial cells migrate from the ventricular zone to the deep cortical plate by radial and tangential migration [30,31].…”

“…These specific clusters at the junctions of the internal capsule with the thalamus, with the external capsule and with the cerebral peduncle, as well as at the junctions of the cerebral peduncle with the optic tract, the medial septum, the periventricular hypothalamic area and the corpus callosum, are transient in the developing brain [30]. In the cortical layers and white matter, microglial cells migrate from the ventricular zone to the deep cortical plate by radial and tangential migration [30,31]. At this time point at about 16–22 weeks of gestation, both the expression of monocyte chemoattractant protein 1 and chemokine macrophage inflammatory protein 1α can be detected in the upper layer of the human cerebral cortex [20,32].…”

“…At this time point at about 16–22 weeks of gestation, both the expression of monocyte chemoattractant protein 1 and chemokine macrophage inflammatory protein 1α can be detected in the upper layer of the human cerebral cortex [20,32]. At 19–30 weeks of gestation, microglia proliferate and accumulate in the semioval center [20,30]. In the mature brain, differences in microglial cell density still exist between different brain regions, with high densities being found in the telencephalon, especially in myelinated regions.…”

Early microglial colonization of the human forebrain and possible involvement in periventricular white‐matter injury of preterm infants

“…These microglia clusters, which are transient structures specific to the developing brain, may be 'waiting sites' for glial cells that have entered the brain and will subsequently colonize the parenchyma (del Rio Hortega, 1932;Innocenti et al 1983a). Their location at meeting points between the main white-matter tracts is highly suggestive of a role in eliminating exuberant axons, promoting neuroaxonal growth, and guiding axonal pathways (Innocenti et al 1983a,b;Perry et al 1985;Chamak et al 1995;Rezaie, 2003). Findings in kittens suggest that the presence of (Innocenti et al 1983a).…”

“…Mononuclear phagocytes penetrate the subpial brain during early embryonic development, before vessel development within the brain parenchyma (Choi, 1981;Cuadros et al 1993;Ling & Wong, 1993;Andjelkovic et al 1998). Several studies have focused on the microglia that are present during various periods of human brain development (Kershman, 1939;Choi, 1981;Fujimoto et al 1989;Esiri et al 1991;Gould & Howard, 1991;Andjelkovic et al 1998;Rezaie & Male, 1999Rezaie, 2003;Rezaie et al 2005;Billiards et al 2006).…”