The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes
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. I...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2011-12-01
|
Series: | Frontiers in Neuroscience |
Subjects: | |
Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2011.00135/full |
id |
doaj-cffe4d7c09664455a734c4226d4077ae |
---|---|
record_format |
Article |
spelling |
doaj-cffe4d7c09664455a734c4226d4077ae2020-11-24T21:18:43ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2011-12-01510.3389/fnins.2011.0013514333The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processesMagen M Johnson0Sharon K Michelhaugh1Mohamad eBouhamdan2Carl J Schmidt3Michael J Bannon4Wayne State University School of MedicineWayne State University School of MedicineWayne State University School of MedicineWayne State University School of MedicineWayne State University School of MedicineThe 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.http://journal.frontiersin.org/Journal/10.3389/fnins.2011.00135/fullhumantranscription factorneurodegenerationNurr1dopamine cellgene expression profile |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Magen M Johnson Sharon K Michelhaugh Mohamad eBouhamdan Carl J Schmidt Michael J Bannon |
spellingShingle |
Magen M Johnson Sharon K Michelhaugh Mohamad eBouhamdan Carl J Schmidt Michael J Bannon The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes Frontiers in Neuroscience human transcription factor neurodegeneration Nurr1 dopamine cell gene expression profile |
author_facet |
Magen M Johnson Sharon K Michelhaugh Mohamad eBouhamdan Carl J Schmidt Michael J Bannon |
author_sort |
Magen M Johnson |
title |
The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes |
title_short |
The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes |
title_full |
The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes |
title_fullStr |
The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes |
title_full_unstemmed |
The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes |
title_sort |
transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2011-12-01 |
description |
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. |
topic |
human transcription factor neurodegeneration Nurr1 dopamine cell gene expression profile |
url |
http://journal.frontiersin.org/Journal/10.3389/fnins.2011.00135/full |
work_keys_str_mv |
AT magenmjohnson thetranscriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT sharonkmichelhaugh thetranscriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT mohamadebouhamdan thetranscriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT carljschmidt thetranscriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT michaeljbannon thetranscriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT magenmjohnson transcriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT sharonkmichelhaugh transcriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT mohamadebouhamdan transcriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT carljschmidt transcriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses AT michaeljbannon transcriptionfactornurr1exertsconcentrationdependenteffectsontargetgenesmediatingdistinctbiologicalprocesses |
_version_ |
1726007866512375808 |