Expression profiling of GABAergic motor neurons in Caenorhabditis elegans

Neurons constitute the most diverse cell types and acquire their identity by the activity of particular genetic programs [1]. The GABAergic nervous system in C. elegans [2] consists of 26 neurons that fall into six classes [3, 4]. Animals that are defective in GABAergic neuron function and development display shrinker movement [5], abnormal foraging and defecation [4, 6]. Among the known shrinker genes, unc-25 and unc47 encode the GABA biosynthetic enzyme glutamic acid decarboxylase and vesicular transporter, respectively [7, 8]. unc-30 encodes a homeodomain protein of the Pitx family and regulates the differentiation of the D-type GABAergic neurons [9]. unc-46 probably functions in presynaptic GABA release [6], but its identity has not been reported. By cell-based microarray analysis, we identified over 250 genes with enriched expression in GABAergic neurons. The highly enriched gene set included all known genes. In vivo expression study with computational predictions further identified six new genes that are potential transcriptional targets of UNC-30. Behavioral studies of a deletion mutant implicate a function of a nicotinic receptor subunit in D-type neurons. Our analysis demonstrates the utility of neuron-specific genomics in identifying cell-specific genes and regulatory networks.