EGL-13 is a Sox domain transcription factor that is required for the maintenance of uterine seam cell fate. Mutant alleles of
egl-13 cause connection-of-gonad and egg-laying defects in C. elegans hermaphrodites. By looking for genetic interactors of
egl-13 , we hope to gain insight into how Sox family members, which are important in many aspects of metazoan development, are regulated and function. We performed a screen for suppressors of the developmental defects of
egl-13 mutants and isolated two such suppressors. Multiple recessive mutations in the gene
him-8 partially suppress the defects caused by incompletely penetrant mutant alleles of
egl-13 . We tested several other him genes, and none of these mutants suppressed the defects of mutant
egl-13 , suggesting that suppression is not an indirect effect of the Him phenotype in general. The
him-8 gene product is haploinsufficient for suppression of
egl-13 , and we conclude that normal HIM-8 protein acts antagonistically to EGL-13. Because null alleles of
egl-13 cannot be suppressed, we conclude that this antagonistic interaction most likely occurs either upstream of EGL-13 or more directly on EGL-13 protein itself. RNAi of
egl-13 in suppressed animals abrogates suppression, consistent with the conclusion that mutant HIM-8 does not bypass the requirement for EGL-13. Furthermore, the addition of multiple copies of the
egl-13 promoter via an integrated transgene array can also abrogate the suppression of egg-laying defects by
him-8 mutations. We are currently investigating the molecular mechanism of suppression and the role of the
egl-13 promoter. In addition to
him-8 , we have isolated a second suppressor of
egl-13 that shows genetic behavior similar to that of suppression by
him-8 , but does not exhibit a Him phenotype. We are currently in the process of mapping and cloning this second gene.