Coordinated Transcriptional Regulation of theunc-25Glutamic Acid Decarboxylase and theunc-47GABA Vesicular Transporter by theCaenorhabditis elegansUNC-30 Homeodomain Protein

Abstract

An important aspect of the specification of neuronal fate is the choice of neurotransmitter. InCaenorhabditis elegansthe neurotransmitter GABA is synthesized by the UNC-25 glutamic acid decarboxylase (GAD) and packaged into synaptic vesicles by the UNC-47 transporter. Bothunc-25andunc-47are expressed in 26 GABAergic neurons of five different types. Previously, we have identified that theunc-30homeobox gene controls the fate of 19 type D GABAergic neurons. We report here that the UNC-30 homeodomain protein transcriptionally regulates the expression ofunc-25andunc-47in the 19 type D neurons. UNC-30 bound to theunc-25andunc-47promoters sequence-specifically. Mutations in the UNC-30 binding sites of theunc-25andunc-47promoters abolished the expression of reporter genes in the D neurons. The ectopic expression of UNC-30 induced the ectopic expression of reporter genes driven by the wild-typeunc-25andunc-47promoters. Our data establish a mechanism for cell type-specific transcriptional coregulation of genes required for the synthesis and packaging of the neurotransmitter GABA.