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.
Highlights
Most often neurogenesis occurs in discrete regions known as germinal or germinative zones (Götz and Huttner, 2005; Franco and Müller, 2013)
ANALYSIS OF CX3CR1-encoding the green fluorescent protein (EGFP)+ CELLS DEPICTS MICROGLIA AS A CELLULAR COMPONENT OF THE EARLY POSTNATAL subventricular zone (SVZ)/rostral migratory stream (RMS) Confocal microscopy analysis of brain sections obtained from newborn mice (P1) reveals that CX3CR1-EGFP+ cells accumulate at the ventricular layers, VZ/SVZ (Figure 1A)
We asked if the CX3CR1-EGFP+ cells observed within the SVZ/RMS niche, olfactory bulb (OB) and in the cortical parenchyma correspond solely to microglial cells, as the fractalkine receptor is expressed by monocytes, subsets of natural killers and dendritic cells (Jung et al, 2000)
Summary
Most often neurogenesis occurs in discrete regions known as germinal or germinative zones (Götz and Huttner, 2005; Franco and Müller, 2013). Interactions of specific cellular and molecular components of the neurogenic niche determine the progeny output (Jones and Wagers, 2008; Pathania et al, 2010; Lim and Alvarez-Buylla, 2014). In the last few years it has been demonstrated that the monocyte counterpart of the nervous system, the microglial cell, is a full component of neurogenic niches (Mercier et al, 2002; Sierra et al, 2010; Olah et al, 2011; Cunningham et al, 2013). Microglia within the CNS parenchyma undergo differentiation, changing from ameboid morphology into ramified cells, rather deceitfully known as resting state (Nimmerjahn et al, 2005). Microglia are involved in several events of brain development, such as phagocytosis, neurito- and synaptogenesis, synaptic pruning, myelination, astrocyte proliferation and differentiation, and vasculogenesis
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