Immediate activation of chemosensory neuron gene expression by bacterial metabolites is selectively induced by distinct cyclic GMP-dependent pathways in C. elegans

Abstract

Dynamic gene expression in neurons shapes fundamental processes of the nervous systems of animals. But how different stimuli that activate the same neuron can lead to distinct transcriptional responses remains unclear. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons of Caenorhabditis elegans. Considering the diverse environmental stimuli that can activate chemosensory neurons of C. elegans, we have sought to understand how specific transcriptional responses can be generated in these neurons in response to distinct cues. We have focused on the mechanism of rapid (<6 min) and selective transcriptional induction of daf-7, a gene encoding a TGF-β ligand that promotes bacterial lawn avoidance, in the ASJ chemosensory neurons in response to the pathogenic bacterium Pseudomonas aeruginosa. Here, we define the involvement of two distinct cyclic GMP (cGMP)-dependent pathways that are required for daf-7 expression in the ASJ neuron pair in response to P. aeruginosa. We show that a calcium-independent pathway dependent on the cGMP-dependent protein kinase G (PKG) EGL-4, and a canonical calcium-dependent signaling pathway dependent on the activity of a cyclic nucleotide-gated channel subunit CNG-2, function in parallel to activate rapid, selective transcription of daf-7 in response to P. aeruginosa metabolites. Our data suggest a requirement for PKG in promoting the fast, selective early transcription of neuronal genes in shaping responses to distinct microbial stimuli in a pair of chemosensory neurons of C. elegans. Author Summary The nervous systems of animals carry out the crucial roles of sensing and interpreting the external environment. When the free-living microscopic roundworm C. elegans is exposed to the pathogenic bacteria Pseudomonas aeruginosa, sensory neurons detect metabolites produced by the pathogen and induce expression of the gene for a neuroendocrine ligand called DAF-7. In turn, activity of DAF-7 is required for the full avoidance response to the P. aeruginosa, allowing the animals to reduce bacterial load and survive longer. Here, we systematically dissect the molecular pathway between the sensation of P. aeruginosa metabolites and the expression of daf-7 in a pair of C. elegans sensory neurons. We show that the intracellular signaling molecule cyclic GMP is a key signaling intermediate. In addition, we show that there are calcium-dependent and calcium-independent pathways that are both required to engage daf-7 expression, highlighting an organizational principle that allows neurons to distinguish between various stimuli.