C. M. Loer Dept. of Biology, Lafayette College, Easton, PA 18042.
We are seeking to identify genes that regulate expression of neurotrans-mitter phenotype of serotonergic neurons in C. elegans. We are using two approaches: 1) isolation and characterization of serotonin-deficient mutants, some of which should identify regulatory genes, and 2) identification of marker genes used by serotonergic neurons, the genes controlled by the regulators of neurotransmitter type.

Among existing serotonin-deficient mutants is cat-4 (e1141), which was first isolated as a dopamine-deficient mutant lacking formaldehyde-induced fluorescence (FIF); it was subsequently found to lack serotonin immuno-reactivity as well (Sulston et al., 1975, J. Comp. Neurol. 163: 215; Desai et al., 1988, Nature 336: 638). Although cat-4 mutant worms were previously described as serotonin hypersensitive, we have found that cat-4 mutants are also hypersensitive to a variety of other unrelated agents. We first noticed that cat-4 mutant worms died much more rapidly than wild type worms during routine "cleaning" of worms with bleach. Whereas wild type worms squirm in bleach for several seconds before becoming rigid, cat-4 mutants stop moving almost instantly (< 1 sec). In addition, cat-4 mutant carcasses seem to disappear or dissolve during this treatment, unlike those of wild type worms. We have further characterized the hypersensitivity of cat-4 mutants to a number of agents, including SDS, levamisole and serotonin. Our observations suggest that mutation of the cat-4 gene affects not only production of neurotransmitters, but also construction of the cuticle. We are currently screening for additional serotonin-deficient mutants based on behavioral abnormalities, bleach hypersensitivity and serotonin immunoreactivity. We hope to identify additional genes that may be involved in expression and regulation of a serotonergic phenotype.