RGD Reference Report - Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons. - Rat Genome Database

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Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons.

Authors: Hwang, DY  Hong, S  Jeong, JW  Choi, S  Kim, H  Kim, J  Kim, KS 
Citation: Hwang DY, etal., J Neurochem. 2009 Dec;111(5):1202-12. Epub 2009 Sep 24.
RGD ID: 5130931
Pubmed: PMID:19780901   (View Abstract at PubMed)
PMCID: PMC4896488   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1471-4159.2009.06404.x   (Journal Full-text)

Midbrain dopamine (mDA) neurons play critical roles in the regulation of voluntary movement and their dysfunction is associated with Parkinson's disease. Pitx3 has been implicated in the proper development of mDA neurons in the substantia nigra pars compacta, which are selectively lost in Parkinson's disease. However, the basic mechanisms underlying its role in mDA neuron development and/or survival are poorly understood. Toward this goal, we sought to identify downstream target genes of Pitx3 by comparing gene expression profiles in mDA neurons of wild-type and Pitx3-deficient aphakia mice. This global gene expression analysis revealed many potential target genes of Pitx3; in particular, the expression of vesicular monoamine transporter 2 and dopamine transporter, responsible for dopamine storage and reuptake, respectively, is greatly reduced in mDA neurons by Pitx3 ablation. In addition, gain-of-function analyses and chromatin immunoprecipitation strongly indicate that Pitx3 may directly activate transcription of vesicular monoamine transporter 2 and dopamine transporter genes, critically contributing to neurotransmission and/or survival of mDA neurons. As the two genes have been known to be regulated by Nurr1, another key dopaminergic transcription factor, we propose that Pitx3 and Nurr1 may coordinately regulate mDA specification and survival, at least in part, through a merging and overlapping downstream pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  ISOTnfrsf1b (Mus musculus)5130931; 5130931mRNA:decreased expression:midbrain and dopaminergic neuron (mouse)RGD 
Parkinson's disease  IEP 5130931mRNA:decreased expression:midbrain and dopaminergic neuron (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnfrsf1b  (TNF receptor superfamily member 1B)

Genes (Mus musculus)
Tnfrsf1b  (tumor necrosis factor receptor superfamily, member 1b)

Genes (Homo sapiens)
TNFRSF1B  (TNF receptor superfamily member 1B)


Additional Information