In Vitro Generation of Dopaminergic Neurons from Adult Subventricular Zone Neural Progenitor Cells

The adult subventricular zone (SVZ) supports a population of cells that display the hallmarks of stem cells: they are self-renewing and multipotent—capable of generating neurons, oligodendrocytes, and astrocytes. In vivo, these adult neural stem cells (aNSCs) are fated primarily for a γ-amino butyric acid (GABA)-ergic lineage of olfactory bulb interneurons, a small subpopulation of which is dopaminergic. Here, we investigate the plasticity of aNSCs in vitro, in particular, their ability to generate a specific neuronal lineage, midbrain dopamine neurons. Previous work using mouse embryonic stem (ES) cells showed that introduction of early developmental inductive cues, sonic hedgehog (SHH) and fibroblast growth factor-8 (FGF-8), directed ES cell-derived neuroepithelial cells to generate midbrain dopaminergic neurons, those lost in Parkinson's disease. Placing aNSCs under similar culture conditions, immunocytochemistry and RT-PCR analysis revealed early dopaminergic neuron specification. However, aNSC-derive...