Uncovering the neuromolecular basis for hygrotaxis in Caenorhabditis elegans

All terrestrial animals must find a proper level of moisture to ensure their health and survival. However, the molecular basis for sensing humidity is unknown in most animals. We used the model nematode Caenorhabditis elegans to uncover a novel mechanism to sense humidity. We found that C. elegans displayed a strong preference, orienting to gradients as shallow as 0.03% relative humidity per mm. Cell-specific ablation and rescue experiments demonstrate that orientation to humidity in C. elegans requires the obligatory combination of distinct mechanosensitive and thermosensitive pathways. The mechanosensitive pathway requires a conserved DEG/ENaC/ASIC mechanoreceptor complex in the FLP neuron pair. Because humidity levels influence the hydration of the worm’s cuticle, our results suggest that FLP may convey humidity information by reporting the degree that subcuticular dendritic sensory branches of FLP neurons are stretched by hydration. The thermosensitive pathway requires cGMP-gated channels in the AFD neuron pair. Because humidity levels affect evaporative cooling, AFD may convey humidity information by reporting thermal flux. Thus, humidity sensation arises as a metamodality in C. elegans that requires the integration of parallel mechanosensory and thermosensory pathways. This hygrosensation strategy, first proposed by Thunberg over 100 years ago, may be conserved because the underlying pathways have cellular and molecular equivalents across a wide range of species including insects and humans. Whereas well-fed worms raised in non-crowded conditions prefer high humidity levels starved worms prefer lower humidity ranges. Our results suggest a model in which social cues from pheromone signaling, along with the worm’s feeding state, influence cyclic guanosine monophosphate (cGMP), peptide, and protein kinase C signaling to produce opposite hygrotaxis behavior.Cellular and Molecular Biolog