Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression

In vitro expanded CNS precursors could provide a renewable source of dopamine (DA) neurons for cell therapy in Parkinson's disease. Functional DA neurons have been derived previously from early midbrain precursors. Here we demonstrate the ability of Nurr1, a nuclear orphan receptor essential for midbrain DA neuron development in vivo , to induce dopaminergic differentiation in naive CNS precursors in vitro . Independent of gestational age or brain region of origin, Nurr1-induced precursors expressed dopaminergic markers and exhibited depolarization-evoked DA release in vitro . However, these cells were less mature and secreted lower levels of DA than those derived from mesencephalic precursors. Transplantation of Nurr1-induced DA neuron precursors resulted in limited survival and in vivo differentiation. No behavioral improvement in apomorphine-induced rotation scores was observed. These results demonstrate that Nurr1 induces dopaminergic features in naive CNS precursors in vitro . However, additional factors will be required to achieve in vivo function and to unravel the full potential of neural precursors for cell therapy in Parkinson's disease.