Many animals possess neurons specialized for the detection of carbon dioxide (CO2), which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO2. The ETS-5 transcription factor is necessary for the specification of CO2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO2-detection and transforms neurons into CO2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO2-sensing neurons in other phyla.

To identify molecular mechanisms that function in G protein signaling, we have performed molecular genetic studies of a simple behavior of the nematode C. elegans, egg laying, which is driven by a pair of serotonergic neurons, the HSNs. The activity of the HSNs is regulated by the Go-coupled receptor EGL-6, which mediates inhibition of the HSNs by neuropeptides. We report here that this inhibition requires one of three inwardly rectifying K+ channels encoded by the C. elegans genome: IRK-1. Using ChannelRhodopsin2-mediated stimulation of HSNs, we observed roles for egl-6 and irk-1 in regulating the excitability of HSNs. Although irk 1 is required for inhibition of HSNs by EGL-6 signaling, we found that other Go signaling pathways that inhibit HSNs involve irk-1 little or not at all. These findings suggest that the neuropeptide receptor EGL-6 regulates the potassium channel IRK 1 is via a dedicated pool of Go not involved in other Go-mediated signaling. We conclude that G protein-coupled receptors that signal through the same G protein in the same cell might activate distinct effectors and that specific coupling of a GPCR to its effectors can be determined by factors other than its associated G proteins.