sli-1, a negative regulator of let-23-mediated signaling in C. elegans.
By screening for suppressors of hypomorphic mutations of let-23, a receptor tyrosine kinase necessary for vulval induction in Caenorhabditis elegans, we recovered > or = 12 mutations defining the sli-1 (suppressor of lineage defect) locus. sli-1 mutations suppress four of five phenotypes associated with hypomorphic alleles of let-23 but do not suppress let-23 null alleles. Thus, a sli-1 mutation does not bypass the requirement for functional let-23 but rather allows more potent LET-23-dependent signaling. Mutations at the sli-1 locus are otherwise silent with respect to vulval differentiation and cause only a low-penetrance abnormal head phenotype. Mutations at sli-1 also suppress the vulval defects but not other defects associated with mutations of sem-5, whose product likely interacts with LET-23 protein during 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 and do not suppress a lin-45 mutation. The sli-1 locus displays dosage sensitivity: severe reduction of function alleles of sli-1 are semidominant suppressors; a duplication of the sli-1(+) region enhances the vulvaless phenotype of hypomorphic mutations of let-23. We propose that sli-1 is a negative regulator that acts at or near the LET-23-mediated 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 fertility and is not regulated by sli-1.
Jongeward
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GD
Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Clandinin
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TR
Sternberg
P W
PW
D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D004303:Dosage Compensation, Genetic; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D005260:Female; D016153:Genes, Suppressor; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics*; D014844:Vulva / Q000196:embryology
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D066246:ErbB Receptors; C085873:let-23 protein, C elegans