GFAP‐GFP neural progenitors are antigenically homogeneous and anchored in their enclosed mosaic niche

Abstract

Study of the different stages of postnatal neurogenesis relies on using antigenic markers and transgenic mice. In particular, neural stem cells that express GFAP are studied using mice expressing GFP under the human GFAP promoter (GFAP‐GFP). However, it remains unclear whether GFP and the commonly used progenitor markers label different cell populations in the neurogenic subventricular zone (SVZ) and its rostral extension into the olfactory bulb (i.e. rostral migratory stream, RMS). Here, we found that all GFP‐fluorescent cells express GFAP, the radial glia marker brain lipid‐binding protein (BLBP), Lewis X (LeX), and the astrocytic marker GLAST. Faint GFP fluorescence could be detected in a few cells expressing EGF receptors (EGFRs), Olig2, or S100, suggesting that GFAP‐GFP cells generate these diverse cell types. GFP‐fluorescent cells were slowly cycling, as shown by their long‐term retention of BrdU, and less than 10% expressed the proliferative markers Ki67 and Mcm2. The majority of EGFR‐expressing cells and Olig2‐expressing cells were cycling. NG2 and EGFR identified distinct progenitor populations while Olig2 labeled a subset of EGFR‐expressing cells. The entire neurogenic zone contained a mosaic of different cell types and was ensheathed by processes of GFAP‐expressing cells and NG2 cells. Finally, using time‐lapse imaging in acute slices, we show that GFP‐fluorescent cells are stationary within the SVZ. Our findings collectively highlight the cellular mosaic of the neurogenic niche, show that the slowly‐cycling GFAP‐expressing cells are stationary and generate distinct intermediate progenitors.