In C. elegans, body size is regulated by sensory perception. Animals lacking sensory inputs, such as a
che-2, grow to a smaller body size, indicating that normal sensory inputs enhance body growth. Here we examined the fat content in such small body mutants by utilizing nile red, a fluorescent dye specific for intracellular lipid droplets, and confocal microscopy with 3D analysis. The total volume of lipid droplets in the intestine, the major fat storage site, was calculated as well as the average intensity of the fluorescence. Based on the amount of fluorescence, we could estimate the total fat content of a worm. The analysis of
che-2 revealed that the animals store more fat than wild type. This phenotype and the small body size phenotype were rescued by introduction of the
che-2 gene. The data indicate that sensory inputs may be involved in energy homeostasis and the allocation of energy for either cell growth or fat storage. Such sensory regulation may be important for animals to adapt to different environmental conditions; if animals do not perceive a rich environment, they may grow to a smaller size and store more fat to survive. We are trying to analyze the relevant neural mechanism by conducting a genetic screen for suppressors of the small body size of
che-2. The suppressors
egl-4,
gcy-12, and
chb-3 were identified and found to encode a cGMP-dependent protein kinase, a guanylyl cyclase and a novel protein, respectively. These mutants exhibit large body size, and the size is not affected by the absence of sensory inputs. The
egl-4 mutation also suppresses the fat accumulation of
che-2. The double mutants between
egl-4,
gcy-12 and
chb-3 do not show additive effects on body size, suggesting that these genes act in the same pathway. The expression of each gene in sensory neurons was sufficient to rescue the body size phenotype. Based on the molecular nature and expression patterns, we speculate that cGMP produced by GCY-12 regulates the activity of EGL-4 cGMP-dependent kinase. GCY-12 tagged with GFP is localized at the sensory cilia. In
chb-3 animals, GCY-12 levels at cilia are decreased. The expression of
chb-3 gene in a specific sensory neuron can restore the GCY-12 localization to cilia in the neuron. Because the expression level of
gcy-12 promoter gfp fusion is not changed in
chb-3, CHB-3 seems to function in GCY-12 trafficking to cilia or protein stabilization. We propose a model where sensory inputs control energy homeostasis and body size through cGMP signaling.