The role of Otx2 in adult mesencephalic-diencephalic dopaminergic neurons

Antonio Simeone, Michela Di Salvio, Luca Giovanni Di Giovannantonio, Dario Acampora, Daniela Omodei, Carmine Tomasetti

Research output: Contribution to journalArticle

Abstract

Mesencephalic and diencephalic dopaminergic (mdDA) progenitors generate two major groups of neurons corresponding to the A9 neurons of the substantia nigra pars compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA). MdDA neurons control motor, sensorimotor and motivated behaviour and their degeneration or abnormal functioning is associated to Parkinson's disease and psychiatric disorders. Although relevant advances have been made, the molecular basis controlling identity, survival and vulnerability to neurodegeneration of SNpc and VTA neurons remains poorly understood. Here, we will review recent findings on the role exerted by the transcription factor Otx2 in adult mdDA neurons. Otx2 expression is restricted to a relevant fraction of VTA neurons and absent in the SNpc. In particular, Otx2 is prevalently excluded from neurons of the dorsal-lateral VTA, which expressed Girk2 and high level of the dopamine transporter (Dat). Loss and gain of function mouse models revealed that Otx2 controls neuron subtype identity by antagonizing molecular and functional features of the dorsal-lateral VTA such as Girk2 and Dat expression as well as vulnerability to the parkinsonian MPTP toxin. Furthermore, when ectopically expressed in the SNpc, Otx2 suppresses Dat expression and confers efficient neuroprotection to MPTP toxicity by suppressing efficient DA uptake.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalMolecular Neurobiology
Volume43
Issue number2
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Dopamine transporter
  • MdDA
  • Otx2
  • Substantia nigra pars compacta
  • Ventral tegmental area

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Simeone, A., Di Salvio, M., Di Giovannantonio, L. G., Acampora, D., Omodei, D., & Tomasetti, C. (2011). The role of Otx2 in adult mesencephalic-diencephalic dopaminergic neurons. Molecular Neurobiology, 43(2), 107-113. https://doi.org/10.1007/s12035-010-8148-y