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Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP.

Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP.

Authors :
Di Salvio, Michela
Di Giovannantonio, Luca Giovanni
Acampora, Dario
Prosperi, Raffaele
Omodei, Daniela
Prakash, Nilima
Wurst, Wolfgang
Simeone, Antonio
Source :
Nature Neuroscience. Dec2010, Vol. 13 Issue 12, p1481-1488. 8p. 2 Color Photographs, 4 Graphs.
Publication Year :
2010

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10976256
Volume :
13
Issue :
12
Database :
Academic Search Index
Journal :
Nature Neuroscience
Publication Type :
Academic Journal
Accession number :
55331059
Full Text :
https://doi.org/10.1038/nn.2661