The
glp-1 and
apx-1 genes encode receptor and ligand respectively, for a cell-cell interaction that specifies the fate of the four cell stage blastomere, ABp. The GLP-1 protein is expressed on the surfaces of sister blastomeres ABa and ABp, and APX-1 is expressed on the surface of the P2 blastomere (Katie Mickie and Jim Priess personal communication). At the four cell stage P2 contacts ABp inducing it to adopt a fate different from its sister cell ABa. The GLP-1 receptor is required again with a different, as yet unidentified, signaling molecule for a second 12-cell stage interaction. GLP-1 and APX-1 have homology to NOTCH and DELTA, receptor and ligand involved in a conserved signaling pathway in Drosophila. The Drosophila suppresser of hairless Su(H) gene encodes a possible transcription factor that represents another conserved component of this signaling pathway. And we have recently confirmed by antisense that a worm Su(H) homolog,
yk60c6 (possibly
lag-1?), can induce an antisense phenotype identical to that of GLP-1, suggesting that worm Su(H) functions along with
glp-1 in both the 4-cell and 12-cell stage interactions. We would like to identify additional genes that are not general components of the signaling pathway but rather function upstream to define the properties of the signaling cell and downstream to define the stage specific outcome of the interaction in the responding cell. In order to identify such genes, we recently screened for new mutations with a phenotype indicating a defect in either the 4-cell or 12-cell stage interaction (but not both). In a screen of 50 thousand haploid genomes we identified seven "
apx-1 like" mutants, in which only the 4-cell stage interaction is affected, and five mutations resembling weak
glp-1 mutants, in which only the 12-cell stage interaction is defective. So far three of the
apx-1 like mutants have been analyzed genetically, and all three represent new mutations in previously known genes,
apx-1,
glp-1 and
skn-2. The new
glp-1(
ne120) allele is interesting in that it is defective in its function at the four cell stage, but can still function at the twelve cell stage (to our knowledge this is the first
glp-1 allele of this type). Skn-2 was known to be required for the P2 cell fate including its ability to signal, however
skn-2 was not known to mutate to an Apx like phenotype. Therefore this new allele may indicate a separate more direct function for
skn-2 in controlling the signaling properties of P2. We are continuing our genetic and phenotypic analysis of the remaining mutations and plan to do further screening in the near future.