In search of new mutants in cell-signaling systems of the nematodeCaenorhabditis elegans

Development of multicellular organisms is controlled mainly by cell-signaling systems. In this review I first discuss methods of genetic analysis and properties of mutants of cell-signaling systems in general and in the nematodeC. elegans. Then, I describe two of our approaches to isolating new mutants in cell-signaling ofC. elegans. The first approach is to select for mutants that have the same visible phenotype as those in known cell-signaling genes. In a survey of larval lethal mutations we found that there are quite a few mutants in which the inner surface of the body wall is detached from the outer surface of the intestine. Some of them map in genes that are known to act in cell-signaling systems in vulval induction or sex myoblast migration, which are not essential to the growth and survival ofC. elegans. Therefore, we think many of the mutations of the above phenotype disrupt cell-signaling in an unidentified essential function, and also cell-signaling in the non-essential functions. The second approach is to isolate mutants resistant to a drug expected to disturb cell-signaling. As the drug we have chosen sodium fluoride, which depletes calcium ion, activates G-proteins and inactivates some phosphatases. The mutants are grouped into two classes (three and two genes, respectively) according to degree of fluoride-resistance and growth rate of larvae. Although there is so far no direct evidence that these mutants are related to cell-signaling, they show complex epistasis that can be explained by a model consisting of a cell-signaling pathway.