The distribution and appearance of microglial cell precursors in the p
renatal hippocampus were examined in embryonic day 14 (E14) to E21 rat
s by nucleoside diphosphatase histochemistry. For comparison, the diff
erentiation of astroglial cells was analyzed from E17 by vimentin and
glial fibrillary acidic protein immunohistochemistry. Based on morphol
ogic features, nucleoside diphosphatase-positive microglial cell precu
rsors were classified as ameboid microglial cells and primitive ramifi
ed microglial cells. Ameboid microglia were present in the hippocampal
primordium on E14. As the hippocampus developed, however, ameboid mic
roglia gradually transformed into primitive ramified microglia, first
recognized at E19. Microglial cell precursors, often related to nucleo
side diphosphatase-labeled blood vessels, were particularly observed n
ext to the pial surface on days E14 and E17 and in the highly vascular
ized area around the hippocampal fissure from E19. Within the brain pa
renchyma, the microglial cell precursors tended to be located within t
he differentiating cell and neuropil layers rather than in the germina
tive zones. The late developing dentate gyrus remained almost devoid o
f microglial cell precursors before birth. Vimentin-positive astroglia
l processes with radial orientation were observed throughout the hippo
campal subregions from E17. In contrast, glial fibrillary acidic prote
in-positive, radial processes were barely discernible in the fimbria a
nd the dentate gyrus before E19. The results are discussed in relation
to the possible interactive role of microglial cells in central nervo
us tissue development and histogenesis. Regarding the origin of hippoc
ampal microglial cell precursors, the present observations support the
view that these cells may well originate from different mesodermal so
urces depending on time and localization. (C) 1997 Wiley-Liss, Inc.