Glial Fibrillary Acidic Protein-expressing Neural Progenitors Give Rise to Immature Neurons Via Early Intermediate Progenitors Expressing Both Glial Fibrillary Acidic Protein and Neuronal Markers in the Adult Hippocampus

Adult neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus, where primary neuronal progenitors that express glial fibrillary acidic protein (GFAP) develop into granule neurons. Here, we used transgenic mice with mouse GFAP promoter-controlled enhanced green fluorescent protein (mGFAP-EGFP Tg mice) to examine how astrocyte-like progenitors differentiate into neuron-committed progenitors. Bromodeoxyuridine (BrdU) analysis indicated that proliferating cells in the neurogenic SGZ transiently expressed EGFP and GFAP, and finally differentiated into cells positive for the neuronal marker, Hu (Hu+). Most proliferating EGFP+ cells showed expression of the stem cell marker, Sox2, and formed clusters of two to four cells containing GFAP+/EGFP+ and GFAP-/EGFP+ cells. No GFAP-/EGFP+ cells were detected in non-neurogenic regions, such as CA1 and CA3 of the pyramidal cell layer. Together with the assumption that exogeneous EGFP has a higher stability than that of endogenous GFAP in the degradation process, it is highly probable that the GFAP-/EGFP+ cells were daughter cells or immediate progeny derived from GFAP+/EGFP+ cells. The subpopulation of proliferating GFAP+/EGFP+ cells expressed proneural protein Mash1 and neuronal marker Hu, while the proliferating GFAP-/EGFP+ cells expressed additional immature neuronal markers, such as polysialic acid-neural cell adhesion molecule (PSA-NCAM) and doublecortin. Therefore, these results suggest that through a few cell divisions, GFAP+ progenitors give rise to neuronal progenitors via neuron-committed early intermediate progenitors that express both GFAP and Hu (and/or Mash1). The findings of the present study also indicated that mGFAP-EGFP Tg mice are useful animals for identifying the daughter cells or immediate progeny derived from GFAP+ neural progenitors.