SLI-1, A NEGATIVE REGULATOR OF LET-23-MEDIATED SIGNALING IN C-ELEGANS

By screening for suppressors of hypomorphic mutations of let-23, a rec eptor tyrosine kinase necessary for vulval induction in Caenorhabditis elegans, we recovered greater than or equal to 12 mutations defining the sli-1 (suppressor of lineage defect) locus. sli-1 mutations suppre ss four of five phenotypes associated with hypomorphic alleles of let- 23 but do not suppress let-23 null alleles. Thus, a sli-1 mutation doe s not bypass the requirement for functional let-23 but rather allows m ore potent LET-SS-dependent signaling. Mutations at the sli-1 locus ar e otherwise silent with respect to vulval differentiation and cause on ly a low-penetrance abnormal head phenotype. Mutations at sli-1 also s uppress the vulval defects but not other defects associated with mutat ions of sem-5, whose product likely interacts with LET-23 protein duri ng vulval induction. Mutations at sli-1 suppress lin-2, lin-7 and lin- 10 mutations but only partially suppress lin-3 and let-60 mutations an d do not suppress a lin-45 mutation. The sli-1 locus displays dosage s ensitivity: severe reduction of function alleles of sli-1 are semidomi nant suppressors; a duplication of the sli-1 (+) region enhances the v ulvaless phenotype of hypomorphic mutations of let-23. We propose that sli-1 is a negative regulator that acts at or near the LET-23-mediate d step of the vulval induction pathway. Our analysis suggests that let -23 can activate distinct signaling pathways in different tissues: one pathway is required for vulval induction; another pathway is involved in hermaphrodite fertilty and is not regulated by sli-1.