Identification of direct Nurr1 target genes having a critical role in dopaminergic neuronal specification and maintenance

Nurr1 is a necessary transcription factor for the differentiation, specification, and maintenance of dopaminergic neurons (DA neurons) in midbrain. DA neurons of the substantia nigra pars compacta degenerate in Parkinson's disease (PD) and Nurr1 gene mutant have been associated with PD. Nurr1 can induce other transcripts, but other downstream effectors are largely unknown. Thus, the goals of this study were to analyze the change in the global gene expression profile of exogenous human Nurr1 expression in human neural stem cells (NSCs). Human NSCs (HB.F3, HB.A4, and HB.F5) that expresses with Nurr1 was utilized to quantitate mRNA levels of various genes. These transcriptional program regulated by Nurr1 was analyzed using oligonucleotide microarrays. Up- or down-regulated genes are functionally related in the migration and synaptogenesis of DA progenitor cells, cell cycle exits during DA cell differentiation. Each genes were validated by real-time PCR in 3 NSCs. Furthermore, we performed RT-PCR analysis of independent mRNA extracted from the ventral midbrain (VMB) of embryonic mice from E9.5 to E13.5. Collectively, our findings indicates the direct evidences that Nurr1 modulates the expression of gene sets which plays important roles in the DA neuron specification and maintenance.