Abstract
Although del Río-Hortega originally reported that leptomeningeal cells are the source of ramified microglia in the developing brain, recent views do not seem to pay much attention to this notion. In this study, in vitro experiments were conducted to determine whether leptomeninges generate ramified microglia. The leptomeninges of neonatal rats containing Iba1+ macrophages were peeled off the brain surface. Leptomeningeal macrophages strongly expressed CD68 and CD163, but microglia in the brain parenchyma did not. Leptomeningeal macrophages expressed epidermal growth factor receptor (EGFR) as revealed by RT-PCR and immunohistochemical staining. Cells obtained from the peeled-off leptomeninges were cultured in a serum-free medium containing EGF, resulting in the formation of large cell aggregates in which many proliferating macrophages were present. In contrast, colony-stimulating factor 1 (CSF1) did not enhance the generation of Iba1+ cells from the leptomeningeal culture. The cell aggregates generated ramified Iba1+ cells in the presence of serum, which express CD68 and CD163 at much lower levels than primary microglia isolated from a mixed glial culture. Therefore, the leptomeningeal-derived cells resembled parenchymal microglia better than primary microglia. This study suggests that microglial progenitors expressing EGFR reside in the leptomeninges and that there is a population of microglia-like cells that grow independently of CSF1.
Highlights
The Spanish scientist who first identified microglia, del Río-Hortega, noted the presence of microglia in early development and proposed that they might initially arise from mesodermal cells of the innermost layer of the meninges, the pia mater
Discussion study demonstrated that the leptomeningeal macrophages of neonatal
This study This demonstrated that the leptomeningeal macrophages of neonatal rats rats generated ramified microglia-like vitro
Summary
The Spanish scientist who first identified microglia, del Río-Hortega, noted the presence of microglia in early development and proposed that they might initially arise from mesodermal cells of the innermost layer of the meninges, the pia mater He reported the migration of embryonic corpuscles from the pia into the nerve centers, but simultaneously proposed that microglia may eventually arise from other related elements, mainly blood-derived monocytes, based on their similarities in morphology and phagocytic activity [1]. These two statements have provoked debate on the origin of microglia in the central nervous system (CNS) for decades. Recent genetic fate-mapping approaches combined with parabiosis have revealed that CNS macrophages arise from yolk sac precursors during embryonic development and remain a stable population [11]
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