Regulation of Body Size and Behavioral State of C. elegans by Sensory Perception and the EGL-4 cGMP-Dependent Protein Kinase

Abstract

The growth and behavior of higher organisms depend on the accurate perception and integration of sensory stimuli by the nervous system. We show that defects in sensory perception in C. elegans result in abnormalities in the growth of the animal and in the expression of alternative behavioral states. Our analysis suggests that sensory neurons modulate neural or neuroendocrine functions, regulating both bodily growth and behavioral state. We identify genes likely to be required for these functions downstream of sensory inputs. Here, we characterize one of these genes as egl-4, which we show encodes a cGMP-dependent protein kinase. We demonstrate that this cGMP-dependent kinase functions in neurons of C. elegans to regulate multiple developmental and behavioral processes including the orchestrated growth of the animal and the expression of particular behavioral states.

Lack of association between polymorphism of the human cyclic GMP-dependent protein kinase gene and obesity

“…4,16 The conserved role of PKG in food-related behavior has been demonstrated in the honey bee Apis mellifera 5 and in the nematode Caenorhabditis elegans. 6 Wu et al (2003) 17 speculated that the product of the for gene might be a component of the Drosophila Neuropeptide F (dNPF) signaling pathway, which regulates food-related behaviors. 18 The dNPF, a homolog of human NPY, is a conserved hypothalamic neuromodulator that strongly increases food intake.…”

“…3 Allelic variation in the homologs of this gene has been linked to differences in food-related behaviors in fruitflies, 4 honey bees 5 and nematodes. 6 In Drosophila melanogaster, the product of the for gene, encoding PKG, might be a component of the Neuropeptide F (a homolog of human Neuropeptide Y (NPY)) signaling pathway, which is involved in regulation of food-related behaviors. 7 Moreover, PKG proteins are highly phylogenetically conserved.…”

Generation and modulation of chemosensory behaviors in C. elegans

“…Animals with compromised chemosensory neuron structure and/or function are small and accumulate fat [25][26][27][28][29]. A TGF-β signaling pathway has been implicated in regulating body size [30], and the DBL-1 TGF-β ligand is neuronally expressed [31].…”

“…A neuroendocrine signal from the chemosensory neurons released in response to external or internal nutrient signals has been proposed to regulate fat storage in the intestine [27][28][29], but pathway components have not yet been defined. As the requirement of chemosensation in regulating body size and fat storage may be independent of the ability of animals to locate food sources or the rate of food consumption and storage, internal metabolic state may be altered by chemosensory perception to regulate cell size and fat metabolism [26,27].…”

“…When placed on a lawn, individual worms exhibit periods of either "dwelling" or "roaming" behavior characterized by low speeds/high turning rate and high speeds/low turning rates, respectively [26]. Mutants with altered chemosensory neuron function spend longer periods in the dwelling vs the roaming state, indicating that the periods spent in each of these states are modulated via chemosensory inputs [26]. Additional motor behaviors regulated by chemosensory inputs from food include egg-laying and pharyngeal pumping [46][47][48][49][50].…”