Vertebrate dopaminergic (DA) neurons play a central role in the coordination of movement, attention, memory and reward. In addition, their dysfuction is linked to Parkinson''s disease or schizophrenia. In C. elegans, DA neurons are involved in behaviors such as egg-laying, defecation, basal motor activity, response to food sources and habituation to touch (Blakely et al. 2006). C. elegans hermaphrodite contains eight DA neurons, four cephalic cells (CEPs), two anterior deirids (ADEs) and two posterior deirids (PDEs). There is a high conservation at a molecular level in the DA system across phylogeny. Specifically, metabolic pathways for catecholamines appear to be conserved from man to worms. Despite the importance of the DA system, little is know in both mammals and C. elegans about the molecular mechanisms that regulate DA cell fate. In this work, we have undertaken an extensive analysis of the promoter region of several of the genes involved in the DA metabolism to try to uncover a hypothetical common cis regulatory element that would control their expression. We have based our analysis in 6 genes: the dopamine transporter (
dat-1) and the tyrosine hydroxylase (
cat-2), both exclusive of DA neurons, the vesicular monoamine transporter (
cat-1), the GTP cyclohydrolase (
cat-4) and the aromatic L-amino acid decarboxylase (
bas-1) expressed in DA and serotonergic cells and the dopamine transporter (
dop-2) expressed in DA neurons and their target cells. In order to identify the promoter elements responsible for DA expression we performed a promoter dissection analysis of all of these genes. We have found a 25 bp sequence in the
dat-1 promoter that is both necessary and sufficient to drive GFP expression specifically in all hermaphrodite DA neurons. Bioinformatics analysis predicted the potential binding of 7 different families of transcription factors. Point mutations in this minimal promoter allowed us to identify the binding site of the ETS transcription factor family as the responsible for DA expression (we have termed this 25bp sequence as the DA motif). All the promoter sequences able to drive DA expression contained predicted DA motifs. Deletion experiments revealed that at least one functional DA motif is necessary for the expression of
cat-1,
cat-2,
cat-4 and
bas-1 genes. There are 10 different ETS genes in C. elegans, with available mutants for all of them. A preliminary analysis of the mutants revealed a loss of
dat-1::gfp expression in one of them,
ast-1 (Schmid et al 2006). We are currently characterizing the role of
ast-1 in DA fate as well as the possible role of other ETS genes.