Our long-range goal is to understand the precise control of gene expression that determines the acquisition of a cell phenotype during development, as well as its maintenance throughout cell life span. We have chosen the ventral dopaminergic neuron as a model, corresponding to tegmental ventral area and sustantia nigra of the mammals central nervous system. These areas are related to voluntary movement control and drug addiction. The transcription factor Nurr1 is essential for the dopaminergic ventral phenotype acquisition; mice null for Nurr1 do not have dopamine in the striatum and died after born, because of motor problems. Nurr1 belongs to the nuclear receptor superfamily, but to the orphan subgroup. It is unknown its target genes in vivo, as well as the control mechanism exerted. Our objective is to determine the molecular mechanism by which Nurr1 controls gene expression. Using the two-hybrid technique we are looking for other coregulators that mediates the transactivation activity of Nurr1. We are also developing studies with reporters coupled to the tyrosine hydroxylase (TH, gene probably regulated by Nurr1) promoter in cell lines in order to find out the relevant elements in the transcriptional regulation of this gene. As well as, we will determine in vivo using chromatin immunoprecipitation assay from dopaminergic ventral tissue the TH gene elements that bind Nurr1. Finally, we are studying the expression of Nurr1 in two models that alter ventral dopaminergic system, such as Parkinson disease and drug addiction.