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Open Access Green as soon as Postprint is submitted to ZB.
Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP.
Nat. Neurosci. 13, 1481-1488 (2010)
Mesencephalic-diencephalic dopaminergic neurons control locomotor activity and emotion and are affected in neurodegenerative and psychiatric diseases. The homeoprotein Otx2 is restricted to ventral tegmental area (VTA) neurons that are prevalently complementary to those expressing Girk2 and glycosylated active form of the dopamine transporter (Dat). High levels of glycosylated Dat mark neurons with efficient dopamine uptake and pronounced vulnerability to Parkinsonian degeneration. We found that Otx2 controls neuron subtype identity by antagonizing molecular and functional features of dorsal-lateral VTA, such as Girk2 and Dat expression. Otx2 limited the number of VTA neurons with efficient dopamine uptake and conferred resistance to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-HCl (MPTP) neurotoxin. Ectopic Otx2 expression also provided neurons of the substantia nigra with efficient neuroprotection to MPTP. These findings indicate that Otx2 is required to specify neuron subtype identity in VTA and may antagonize vulnerability to the Parkinsonian toxin MPTP.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
MIDBRAIN DOPAMINERGIC-NEURONS; MURINE MUTATION WEAVER; PARKINSONS-DISEASE; GENE-EXPRESSION; MICE LACKING; TRANSPORTER; FATE; BRAIN; DEATH; PITX3
Language
english
Publication Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
1097-6256
e-ISSN
1546-1726
Journal
Nature Neuroscience
Quellenangaben
Volume: 13,
Issue: 12,
Pages: 1481-1488
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)
POF-Topic(s)
30204 - Cell Programming and Repair
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-500500-001
PubMed ID
21057506
DOI
10.1038/nn.2661
Erfassungsdatum
2010-12-08