Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-90 homeodomain protein

An important aspect of the specification of neuronal fate is the choice of neurotransmitter. In Caenorhabditis elegans the neurotransmitter GABA is sy nthesized by the UNC-25 glutamic acid decarboxylase (GAD) and packaged into synaptic vesicles by the UNC-47 transporter. Both unc-25 and unc-47 are ex pressed in 26 GABAergic neurons of five different types. Previously, we hav e identified that the unc-30 homeobox gene controls the fate of 19 type D G ABAergic neurons. We report here that the UNC-30 homeodomain protein transc riptionally regulates the expression of unc-25 and unc-47 in the 19 type D neurons. UNC-30 bound to the unc-25 and unc-47 promoters sequence-specifica lly. Mutations in the UNC-30 binding sites of the unc-25 and unc-47 promote rs abolished the expression of reporter genes in the D neurons. The ectopic expression of UNC-30 induced the ectopic expression of reporter genes driv en by the wild-type unc-25 and unc-47 promoters. Our data establish a mecha nism for cell type-specific transcriptional coregulation of genes required for the synthesis and packaging of the neurotransmitter GABA.