Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis

In the course of adult hippocampal neurogenesis, new cells go through a series of stages associated with proliferative activity. The most highly proliferative cell type is an intermediate precursor cell, called type-2 cell. We here report that on the level of type-2 cells a transition takes place between features associated with the glial and the neuronal lineage. We show that stem-cell marker Sox2 and radial glia marker BLBP are expressed in type-2 cells but label only a small percentage of the proliferating cells. By and large, precursor cell marker Sox2 was found to be widely expressed in hippocampal astrocytes. Between 3 h and 1 week after a single injection of permanent S-phase marker bromodeoxyuridine (BrdU), the number of BrdU-labeled BLBP-positive cells did not change, consistent with the idea that both markers here are associated with the maintained precursor cell pool. Using reporter gene mice expressing the green fluorescent protein (GFP) under the promoter for nestin we found an overlap of GFP with markers of the neuronal lineage, doublecortin (DCX) and transcription factor NeuroD1 in type-2 cells, whereas in glial fibrillary acidic protein (GFAP)-GFP mice expression of GFP and NeuroD1 or DCX was mutually exclusive. Electrophysiologically, the group of type-2 cells fell into two subgroups: one with astrocytic properties and another with an early "complex" phenotype of neural progenitor cells. Our data further support the existence of proliferative precursor cells that mark the transition between glia-like states and neuronal differentiation.