Lineage progression from stem cells to new neurons in the adult brain ventricular-subventricular zone

It has been estimated that ~10,000 new neurons are generated daily in the mouse ventricular-subventricular zone (V-SVZ), an extensive germinal niche present in the walls of the lateral brain ventricles in many adult mammals. Neural stem cells, a subpopulation of GFAP-expressing astrocytes (B1 cells), contact the ventricle with a small apical process surrounded by ependymal cells forming pinwheel-like structures. B1 cells generate intermediate progenitors (C cells), which differentiate into neuroblasts (A cells). A cells also divide and migrate out of the V-SVZ along the rostral migratory stream into the olfactory bulb, where they differentiate into local interneurons. A full understanding of this process requires precise information of the dynamics of proliferation of V-SVZ progenitor populations and how many times each divides. This information is now available for the adult mouse brain. The reporter protein in hGFAP::GFP mice was used to identify B1 cells and immunolabeling for Ascll, and DCX was used to identify C and A cells, respectively. Of the Ascll + cells, only 3.1+/−0.6% were also GFP+, while 15.9+/−1.6% were DCX+, indicating a small overlap between populations, possibly associated to transitional stages between cell types. We used whole-mount preparations, which provide an en face view of the lateral ventricular surface, to analyze the entire neurogenic niche, minimizing the effect of rostral migration of proliferating progenitors on our quantifications. Using a combination of thymidine analogs (CldU and EdU) and Lineage progression from stem cells to new neurons in the adult brain ventricular-subventricular zone