Terminal Differentiation of Mesodiencephalic Dopaminergic Neurons:

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The orphan nuclear hormone receptor Nurr1 and the homeobox Pitx3 were the first two transcription factors that were implicated in the development of mesodiencephalic dopaminergic (mdDA) neurons.1,2 These factors have their own expression profile in the brain: Nurr1 is expressed in many forebrain regions, whereas Pitx3 is exclusively expressed in mdDA neurons. Functional analysis of the respective mouse mutants have emphasized the importance of both factors for mdDA development and their difference in mode of action: Nurr1 has been implicated particularly in specifying the dopaminergic neurotransmitter phenotype and in neuronal maintenance, while Pitx3 is essential for the development of a subset of mdDA neurons encompassing the SNc. Recent data on molecular mechanisms of action and regulation of target genes reveal a large complexity and suggest that Nurr1 and Pitx3 are part of extended regulatory networks. In this chapter we highlight the molecular programming of mdDA neurons3 4 from the viewpoint of Pitx3 and Nurr1.