Ontogeny of CX3CR1-EGFP expressing cells unveil microglia as an integral component of the postnatal subventricular zone

Abstract

The full spectrum of cellular interactions within CNS neurogenic niches is still poorly understood. Only recently has the monocyte counterpart of the nervous system, the microglial cells, been described as an integral cellular component of neurogenic niches. The present study sought to characterize the microglia population in the early postnatal subventricular zone (SVZ), the major site of postnatal neurogenesis, as well as in its anterior extension, the rostral migratory stream (RMS), a pathway for neuroblasts during their transit toward the olfactory bulb (OB) layers. Here we show that microglia within the SVZ/RMS pathway are not revealed by phenotypic markers that characterize microglia in other regions. Analysis of the transgenic mice strain that has one locus of the constitutively expressed fractalkine CX3CR1 receptor replaced by the gene encoding the enhanced green fluorescent protein (EGFP) circumvented the antigenic plasticity of the microglia, thus allowing us to depict microglia within the SVZ/RMS pathway during early development. Notably, microglia within the early SVZ/RMS are not proliferative and display a protracted development, retaining a more immature morphology than their counterparts outside germinal layers. Furthermore, microglia contact and phagocyte radial glia cells (RG) processes, thereby playing a role on the astroglial transformation that putative stem cells within the SVZ niche undergo during the first postnatal days.

Ischemic preconditioning induces cortical microglial proliferation and a transcriptomic program of robust cell cycle activation

“…This results in expression of eGFP in CX3CR1 + cells, which include microglia, dendritic cells, and activated endothelial cells (Jung et al, ). This transgenic mouse line and related variants, such as the cell type specific knockdown Cx3cr1 Cre and the conditional tamoxifen‐inducible Cx3cr1 CreER lines (Goldmann et al, ), are commonly used in studies that necessitate a reliable pan‐microglial marker, especially as microglia may exhibit some degree of antigenic plasticity and markers for myeloid cells often overlap with those of microglia (Xavier, Lima, Nedergaard, & Menezes, ).…”

Developmental changes in microglial mobilization are independent of apoptosis in the neonatal mouse hippocampus

“…Moreover, despite widespread cell proliferation (BrdU uptake) in the developing mouse brain, microglial proliferation in the neurogenic niche during the first postnatal week was reported to be very low (Xavier et al 2015). It remains to be determined whether this also holds true for hippocampal microglia during the first postnatal week in vivo .…”

Microglial subtypes: diversity within the microglial community

“…The use of CX3CR1 ‐EGFP reporter mice, in which one of the loci of fractalkine receptor Cx3cr1 is replaced by the gene encoding EGFP, revealed heterogeneity of the microglial cell population within the neurogenic subventricular zone (SVZ), and the adjacent rostral migratory stream (RMS) that terminates into the OB (Ribeiro Xavier et al , ; Xavier et al , ; Fig ). First, it was noticed that microglia located along the SVZ‐RMS‐OB axis are significantly less ramified than microglia from adjacent areas in mice and rats (Shigemoto‐Mogami et al , ; Ribeiro Xavier et al , ; Xavier et al , ). CX3CR1 ‐EGFP expressing microglia were TREM2‐negative, and about half of them also IBA1‐negative in the SVZ and RMS of wild‐type adult mice.…”

“…As observed in the SVZ and RMS, IBA1‐negative and IBA1‐positive microglia were also observed in close vicinity to another within the OB. Of note, the antigenic heterogeneity of CX3CR1 ‐EGFP expressing microglia was reported in later development among the SVZ of newborn (P1) and early postnatal (P7) mice, suggesting persistence of these microglial cell populations beyond ontogeny (Xavier et al , ). In addition, at those developmental ages, CD68 expression was detected in a microglial subset only.…”