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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
MIDBRAIN DOPAMINERGIC-NEURONS; MURINE MUTATION WEAVER; PARKINSONS-DISEASE; GENE-EXPRESSION; MICE LACKING; TRANSPORTER; FATE; BRAIN; DEATH; PITX3
ISSN (print) / ISBN
1097-6256
e-ISSN
1546-1726
Zeitschrift
Nature Neuroscience
Quellenangaben
Band: 13,
Heft: 12,
Seiten: 1481-1488
Verlag
Nature Publishing Group
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Developmental Genetics (IDG)