The mesencephalic dopaminergic (mesDA) neurons playa relevant role in the control of movement,behaviourand cognition. Indeedlossand/or abnormal development of mesDA neurons is responsiblefor Parkinson'sdiseaseas well as for addictive and psychiatric disorders. A wealth of information has been provided on gene functions involved in the molecular mechanism controlling identity, fate and survival of mesDA neurons. Collectively, these studies are contributing to a growing knowledge of the genetic networks required for proper mesDA development, thus disclosing new perspectives for therapeutic approaches of mesDA disorders. Here we will focus on the control exerted by Otx genesin early decisions regulating the differentiation of progenitors located in the ventral midbrain. In this context, the regulatory network involving Otx functional interactions with signalling molecules and transcription factors required to promote or prevent the development ofmesDA neurons will be analyzed in detail.