The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes

• Main Authors: Magen M Johnson, Sharon K Michelhaugh, Mohamad eBouhamdan, Carl J Schmidt, Michael J Bannon
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2011-12-01
• Series: Frontiers in Neuroscience
• Subjects: human; transcription factor; neurodegeneration; Nurr1; dopamine cell; gene expression profile
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fnins.2011.00135/full

The transcription factor nurr1 plays a pivotal role in the development and maintenance of neurotransmitter phenotype in midbrain dopamine neurons. Conversely, decreased nurr1 expression is associated with a number of dopamine-related CNS disorders, including Parkinson’s disease and drug addiction. In order to better understand the nature of nurr1-responsive genes and their potential roles in dopamine neuron differentiation and survival, we used a neural cellular background in which to generate a number of stable clonal lines with graded nurr1 gene expression that approximated that seen in DA cell-rich human substantia nigra. Gene expression profiling data from these nurr1-expressing clonal lines were validated by quantitative RT-PCR and subjected to bioinformatic analyses. The present study identified a large number of nurr1-responsive genes and demonstrated the potential importance of concentration-dependent nurr1 effects in the differential regulation of distinct nurr1 target genes and biological pathways. These data support the promise of nurr1-based CNS therapeutics for the neuroprotection and/or functional restoration of DA neurons.