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The Journal of Neuroscience, August 1, 1999, 19(15):6225-6234
Coordinated Transcriptional Regulation of the unc-25 Glutamic Acid Decarboxylase and the unc-47 GABA Vesicular Transporter by the Caenorhabditis elegans UNC-30 Homeodomain Protein
Catharine Eastman1, H. Robert Horvitz2, and Yishi Jin1, 2 1 Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, California 95064, and 2 Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
An important aspect of the specification of neuronal fate is the choice of neurotransmitter. In Caenorhabditis elegans the neurotransmitter GABA is synthesized 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 expressed in 26 GABAergic neurons of five different types. Previously, we have identified that the unc-30 homeobox gene controls the fate of 19 type D GABAergic neurons. We report here that the UNC-30 homeodomain protein transcriptionally 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-specifically. Mutations in the UNC-30 binding sites of the unc-25 and unc-47 promoters 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-type unc-25 and unc-47 promoters. Our data establish a mechanism for cell type-specific transcriptional coregulation of genes required for the synthesis and packaging of the neurotransmitter GABA.
Key words: C. elegans; homeodomain; transcription; GABA; GAD; GABA transporter
Copyright © 1999 Society for Neuroscience 0270-6474/99/19156225-10$05.00/0
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