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Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons

ABSTRACT: Nurr1 (Nr4a2, nuclear receptor subfamily 4 group A member 2) is needed for the development of ventral midbrain dopaminergic neurons, and has been associated with Parkinson's disease. We used mice where the Nurr1 gene is ablated by tamoxifen treatment selectively in dopaminergic neurons. As a control, we used tamoxifen-treated mice where Nurr1 is not ablated. By laser microdissection of neurons selected by their TH1 (Th1l, TH1-like homolog) gene expression, we selected dopaminergic neurons for RNA extraction and high-throughput mRNA sequencing, in order to identify genes regulated by Nurr1. We found the main functional category of Nurr1-regulated genes are the nuclear-encoded mitochondrial genes. Dopaminergic neurons with or without Nurr1 knocked out. TH-positive neurons were laser capture microdissected from cryostat coronal sections of the midbrain.

ORGANISM(S): Mus musculus

SUBMITTER: Daniel Ramsköld 

PROVIDER: E-GEOD-42912 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons.

Kadkhodaei Banafsheh B   Alvarsson Alexandra A   Schintu Nicoletta N   Ramsköld Daniel D   Volakakis Nikolaos N   Joodmardi Eliza E   Yoshitake Takashi T   Kehr Jan J   Decressac Mickael M   Björklund Anders A   Sandberg Rickard R   Svenningsson Per P   Perlmann Thomas T  

Proceedings of the National Academy of Sciences of the United States of America 20130122 6

Developmental transcription factors important in early neuron specification and differentiation often remain expressed in the adult brain. However, how these transcription factors function to mantain appropriate neuronal identities in adult neurons and how transcription factor dysregulation may contribute to disease remain largely unknown. The transcription factor Nurr1 has been associated with Parkinson's disease and is essential for the development of ventral midbrain dopamine (DA) neurons. We  ...[more]

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