Cited by 118Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurogenesis and neuroplasticity mechanisms

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

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Di Salvio, Michela, Di Giovannantonio, Luca Giovanni, Acampora, Dario, Prosperi, Raffaele, Omodei, Daniela, Prakash, Nilima, Wurst, Wolfgang, Simeone, Antonio·2010·Nature Neuroscience

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.

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Crossref · 10.1038/nn.2661

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Authors
Di Salvio, M., Di Giovannantonio, L. G., Acampora, D., Prosperi, R., Omodei, D., Prakash, N., Wurst, W., & Simeone, A.
Affiliations
  • European School of Molecular Medicine (IT)
  • University of Sannio (IT)
  • CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT)
  • Helmholtz Munich (DE)
Venue
Nature Neuroscience
Published
2010-11-07
Volume
13
Issue
12
Pages
1481-1488
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W1993634104
Cited by
118
References
50
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 11 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 3 · 2018: 5 · 2017: 12 · 2016: 5 · 2015: 13 · 2014: 12 · 2013: 11 · 2012: 8
FWCI
5.52
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Site cant be reached (submittedVersion)
  • DZNE Pub (submittedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
Otx2, ventral tegmental area, MPTP-induced neurotoxicity, Parkinson's disease, dopaminergic neurons, GIRK2, dopamine transporter, substantia nigra, neuroprotection, homeoproteins, dopamine uptake
MeSH terms
Animals, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Neurons, Ventral Tegmental Area, MPTP Poisoning, Mice, Otx Transcription Factors, Embryonic Stem Cells

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