In vitro generation of mature dopamine neurons by decreasing and delaying the expression of exogenous Nurr1

Abstract

Neural stem/progenitor cell (NSC/NPC) cultures can be a source of dopamine (DA) neurons for experimental and transplantationpurposes. Nurr1, a steroid receptor transcription factor, can overcome the limitations associated with differentiation of cultured NPCsinto DA neurons. However, forced Nurr1 expression in NPC cultures generates non-neuronal and/or immature DA cells. We showhere that the Nurr1 level and period of expression crucially affect the differentiation and maturation of Nurr1-induced DA neurons.Mature DA neurons were generated by manipulating Nurr1 expression patterns to resemble those in the developing midbrain.