GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain

Abstract

Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

“…Moreover, the number of those cells was twice as high in the paroxetine-treated mice. According to the study of Garcia et al (2004), this indicates that the double-labeled cells of the subgranular zone are GFAP-expressing neural progenitors and supports the notion that increased neurogenesis occurs in hippocampi of chronically paroxetine-treated mice.…”

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

“…DCX has become a widely used marker for newly generated neuroblasts in proliferative zones in adult 14,31,53,54 . In these regions, DCX is expressed exclusive of GFAP positive cells, and appears to be one of the earliest markers for cells transitioning from astrocytic glia to neuroblasts in the SVZ and RMS 32 .…”

“…These neurons translocate using a process known as chain migration, whereby the cells use each other as the migratory substrate 12 . These newly generated neurons are derived from SVZa glial fibrillary acidic protein (GFAP)-positive astrocytes 13,14 , which also ensheath them as they move through extensive interconnected networks along the lining of the lateral ventricle in the rostral forebrain and the rostral migratory stream (RMS) 15 . There, they are under the control of extracellular migration guidance cues, including the secreted ligands Slit and Reelin [16][17][18][19] , the receptors ErbB4 and Deleted in Colorectal Carcinoma (DCC) 20,21 , as well as integrins and neural cell adhesion molecule [21][22][23] .…”

Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon

“…In the adult mammalian brain, two regions display neurogenic potential: The subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus located in the hippocampus harbour neural stem cells with astrocytic features generating predominantly neurons (Doetsch et al, 1999;Gage, 2000;Seri et al, 2001;Alvarez-Buylla and Garcia-Verdugo, 2002;Kempermann, 2002;Garcia et al, 2004). In contrast, more than 16 discrete sites produce new neurons in the brain of an adult zebrafish Grandel et al, 2006).…”