Specification of muscle neurotransmitter sensitivity by a paired-like homeodomain protein in Caenorhabditis elegans

The effects of neurotransmitters depend on the receptors expressed on the target cells. In Caenorhabditis elegans, there are two types of GABA receptors that elicit opposite effects: excitatory receptors that open cation-selective channels, and inhibitory receptors that open anion-selective channels. The four non-striated enteric muscle cells required for the expulsion step of the defecation behavior are all sensitive to GABA: the sphincter muscle expresses a classical GABA-sensitive chloride channel (UNC-49) and probably relaxes in response to GABA, while the other three cells express a cation-selective channel (EXP-1) and contract. Here we show that the expression of the exp-1 gene is under the control of dsc-1, which encodes a Paired-like homeodomain protein, a class of transcription factors previously associated with the terminal differentiation of neurons in C. elegans. dsc-1 mutants have anatomically normal enteric muscles but are expulsion defective. We show that this defect is due to the lack of expression of exp-1 in the three cells that contract in response to GABA. In addition, dsc-1, but not exp-1, affects the periodicity of the behavior, revealing an unanticipated role for the enteric muscles in regulating this ultradian rhythm.