Origin of microglia

This paper reviews the various proposed hypotheses on the origin of microgl ia. The seminal study of del Rio-Hortega first stated that the cells were d erived from the mesodermal pial cells that invaded the brain during embryon ic development. Along with this was the description of precursor cells in t he yolk sac in early development. Our results in the embryonic mouse brain have shown the occurrence of lectin-labelled precursor cells at the yolk sa c that later appeared in the mesenchymal tissue associated with the neuroep ithelium where they penetrated the nervous tissue to become the microglia. A second major view has held that microglia are of neuroectodermal origin; the cells either originate from glioblasts or the germinal matrix. Another school of thought is that microglia are derived from blood monocytes. In th is connection, circulating monocytes enter the developing brain to assume t he form as amoeboid microglia that subsequently evolve to become the ramifi ed microglia. In traumatic brain lesions following an intravenous injection of colloidal carbon as a cytoplasmic marker for monocytes, it was found th at carbon-labelled monocytes were the main source of brain macrophages, som e of which transformed into microglia during the healing process. In conclu sion, our results derived from the normal and altered brain development as well as from experimental lesions tend to favour the view of the monocytic nature of microglia. Recent studies by us also point to the possibility tha t some microglial cells may arise from the pial mesenchymal macrophages tha t appear to originate from the yolk sac precursors. (C) 2001 Wiley-Liss. In c.