Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain

Microglia, the resident CNS macrophages, represent about 10% of the adult b rain cell population. Although described a long time ago, their origin and developmental lineage is still debated. While del Rio-Hortega suggested tha t microglia originate from meningeal macrophages penetrating the brain duri ng embryonic development, many authors claim that brain parenchymal microgl ia derive from circulating blood monocytes originating from bone marrow. We have previously reported that the late embryonic and adult mouse brain par enchyma contains potential microglial progenitors [F. Alliot, E. Lecain, B. Grima, B. Pessac, Microglial progenitors with a high proliferative capacit y in the embryonic and the adult mouse brain, Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 1541-1545]. We now report that they can be detected in the brain rudiment from embryonic day 8, after their appearance in the yolk sac and that their number increases until late gestation. We also show that microgl ia appear during embryonic development and that their number increases stea dily during the first two postnatal weeks, when about 95% of microglia are born. Finally, the main finding of this study is that microglia is the resu lt of in situ proliferation, as shown by the high proportion of parenchymal microglial cells that express PCNA, a marker of cell multiplication, in em bryonic and postnatal brain. Taken together, our data support the hypothesi s that terminally differentiated brain parenchymal microglia are derived fr om cells originating from the yolk sac whose progeny actively proliferates in situ during development. (C) 1999 Published by Elsevier Science B.V. All rights reserved.