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

Antonio Simeone (1) , Michela Di Salvio (1) , Luca Giovanni Di Giovannantonio (1) , Dario Acampora (1) , Raffaele Prosperi (1) , Daniela Omodei (1) , Nilima Prakash (1) , Wolfgang Georg Wurst (1)

1 Developmental neurobiology

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 prevalently complementary to those expressing Girk2 and glycosylated active form of Dopamine transporter (Dat). High level of glycosylated-Dat identifies 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. Through this control, Otx2 limits the number of VTA neurons with efficient Dopamine uptake and confers resistance to the MPTP neurotoxin. Ectopic Otx2 expression also provides neurons of the Substantia Nigra with efficient neuroprotection to MPTP. These findings show that Otx2 is required to specify neuron subtype identity in VTA and may antagonize vulnerability to the Parkinsonian toxin MPTP.

Mots clés: Neurodegeneration; Development

Antonio Simeone, Michela Di Salvio, Luca Giovanni Di Giovannantonio, Dario Acampora, Raffaele Prosperi, et al.. Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP. Nature Neuroscience, 2010, ⟨10.1038/nn.2661⟩. ⟨hal-00591155⟩