The
glp-1 gene product is involved in numerous cell signalling events that determine cell fate during development in C. elegans. In particular,
glp-1 plays an important role in germline development, regulating the decision between continued mitotic proliferation and entry into meiosis. Germline cells that receive a signal from the distal tip cell (DTC), a somatic cell, remain in mitosis; those that do not receive the signal enter meiosis. Mutations in
glp-1 disrupt the signaling pathway leading to reduced proliferation of the germ-line which in turn leads to reduced fertility or sterility, depending on the level of proliferation produced by a particular
glp-1 allele. Genetic, molecular, and immunocytochemical data strongly suggest that GLP-1 is a transmembrane receptor. Although GLP-1 has been relatively well-studied and putative GLP-1 ligands have been identified (e.g. LAG-2), very little is known about the rest ofthe GLP-1 signal transduction pathway. Numerous suppressors and enhancers of
glp-1 have been identified as one strategy to identify other genes involved in this signalling pathway. Mutations in sog (suppressor of
glp-1) genes suppress glp- 1(ts) mutations by an unknown mechanism. All of the known sog mutations lack an obvious phenotype beyond suppression of
glp-1(ts) alleles with the exception of
sog-10, which has a cold-sensitive Fog (feminization of the germline) phenotype. In contrast, mutations in enhancer genes exacerbate the effect of
glp-1 mutations by further reducing proliferation in the germline. The genes that carry these enhancer mutations are called ego (enhancer of
glp-1) genes. In addition, certain alleles of two previously identified genes,
lag-1 and
glp-4, have an Ego phenotype. All of the ego mutations that have been identified cause reduced proliferation or other germline defects, sterility, or lethality in
glp-1(+) animals. To better understand the role of sog and ego genes in
glp-1 signaling, we are constructing sog(-); ego(-) double mutants using different combinations of sog and ego mutations. In particular, we would like to know if any of the sog mutations are able to suppress the sterility, lethality, reduced proliferation of germline cells, and other germline defects associated with ego mutations. At least one ego gene,
lag-1, is likely to be directly involved in the
glp-1 signaling pathway based on several independent lines of evidence. The roles of the other ego genes in the pathway are not known. As a result, information about whether these mutations interact with one another would be useful in clarifying their roles in the
glp-1 signaling pathway. We are in the process of making double mutants carrying one of the two most interesting ego genes,
ego-3 and
lag-1, and one of a subset of the sog genes.
ego-3 is of interest because of the very unusual effects it has in the germline, e.g. proximal proliferation, and
lag-1 is probably directly involved in
glp-1 signaling. Double mutants will be compared with single mutant controls with respect to brood size, embryonic/larval lethality, and germline morphology and proliferation.