Molecular Neurobiology

, Volume 43, Issue 2, pp 107–113

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
Article

DOI: 10.1007/s12035-010-8148-y

Cite this article as:
Simeone, A., Di Salvio, M., Di Giovannantonio, L.G. et al. Mol Neurobiol (2011) 43: 107. doi:10.1007/s12035-010-8148-y

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.

Keywords

Otx2mdDADopamine transporterVentral tegmental areaSubstantia nigra pars compacta

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Antonio Simeone
    • 1
    • 2
  • Michela Di Salvio
    • 1
  • Luca Giovanni Di Giovannantonio
    • 1
  • Dario Acampora
    • 1
    • 2
  • Daniela Omodei
    • 1
  • Carmine Tomasetti
    • 1
  1. 1.CEINGE Biotecnologie Avanzate, and SEMM European School of Molecular MedicineNaplesItaly
  2. 2.Institute of Genetics and Biophysics “A. Buzzati-Traverso”, CNRNaplesItaly