The Gene Expressed in a Subset of Dopaminergic Neurons Regulates Locomotion in .

CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the () gene, an orthologue of mammalian CD133 in , plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of in locomotion. Both mutants and pan-neuronal inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in mutant and pan-neuronal inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, mutant and pan-neuronal inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in .