In C. elegans , body size may be regulated by the nervous system. Lewis and Hodgkin initially reported that cilium-defective mutants such as
che-2 and
che-3 are smaller than wild-type animals. A smaller body size is also observed in other cilium-defective mutants and in the
tax-4 mutant (
tax-4 encodes a cGMP-gated channel that is necessary for chemosensation). These observations suggest that if an animal cannot sense an environmental cue such as food, body size may be reduced through altered neural activity. Such regulation may be useful if a smaller body is economical. In order to analyze the putative neural regulation of body size, we isolated suppressor mutants of the ch e-2 small b ody size phenotype ( chb ). 15,000 haploid genomes were screened, yielding 28 candidates. None of these mutants suppresses the dye-filling defect of
che-2 . Some of these suppressors show the same body size with or without the
che-2 mutation in the background, suggesting that they have possible defects downstream of sensory signals. In this class (9 of 28),
chb-1 ,
chb-2 ,
chb-3 and
chb-4 have been mapped to chromosomes IV, II, I and V respectively, using the snipSNP method (thanks to Wicks and Plasterk). In the course of mapping of
chb-1 , we found that
chb-1 is allelic with
odr-9/egl-4 by complementation testing. The phenotype of
odr-9/egl-4 is well characterized and reported (S. Daniels et al. 2000).
chb-1 shares with
odr-9/egl-4 all of these phenotypes including a chemotaxis defect, an egg-laying defect, dauer formation at 27 C, and aldicarb-resistance. We identified the
chb-1 gene by rescuing with cosmids and cDNA as well as by mutation site analysis. This gene encodes a cGMP-dependent protein kinase. There are at least 2 different promoter regions for this gene (a and b). We have found that the a. promoter region can direct expression in 10 pairs of head neurons, and the b. promoter region can direct the expression in body wall muscle. We found that the cDNA driven by the a. promoter is sufficient to rescue the suppressor phenotype of
che-2 small body size and all other known phenotypes, and that the cDNA driven by the b. promoter has no rescuing ability. The fact that a cDNA driven by a panneuronal promoter, H20 (thanks to Ishihara and Katsura), can also rescue all phenotypes supports a model in which this gene acts in the nervous system. Interestingly, the a. promoter does not direct expression in chemosensory neurons such as AWA, AWC, and ASE. Although we cannot exclude the possibility of a low level of expression in these neurons, this may suggest that the role of this gene is in the interneurons downstream of the sensory neurons required for chemotaxis In conclusion, we propose a model in which the body size of worms is regulated through sensory signaling, and a cGMP-dependent protein kinase is involved in the downstream processing of this sensory information.