sli-3 Negatively Regulates the LET-23/Epidermal Growth Factor Receptor-Mediated Vulval Induction Pathway in Caenorhabditis elegans
Abstract
The LIN-3–LET-23-mediated inductive signaling pathway plays a major role during vulval development in C. elegans. Studies on the components of this pathway have revealed positive as well as negative regulators that function to modulate the strength and specificity of the signal transduction cascade. We have carried out genetic screens to identify new regulators of this pathway by screening for suppressors of lin-3 vulvaless phenotype. The screens recovered three loci including alleles of gap-1 and a new gene represented by sli-3. Our genetic epistasis experiments suggest that sli-3 functions either downstream or in parallel to nuclear factors lin-1 and sur-2. sli-3 synergistically interacts with the previously identified negative regulators of the let-23 signaling pathway and causes excessive cell proliferation. However, in the absence of any other mutation sli-3 mutant animals display wild-type vulval induction and morphology. We propose that sli-3 functions as a negative regulator of vulval induction and defines a branch of the inductive signaling pathway. We provide evidence that sli-3 interacts with the EGF signaling pathway components during vulval induction but not during viability and ovulation processes. Thus, sli-3 helps define specificity of the EGF signaling to induce the vulva.
Additional Information
© 2006 by the Genetics Society of America. Manuscript received July 26, 2006; Accepted for publication August 21, 2006. We thank Neil Hopper, Chieh Chang, Giovanni Lisa, Maureen Barr, and Minqin Wang for insights in this project. We also thank the anonymous reviewers for helpful comments on a draft of this article. This work was supported by the U.S. Public Health Service (USHS) grant HD23690 to P.W.S., the Canada Research Chair and McMaster research funds to B.P.G., and National Institutes of Health grant R01 GM073184 to N.M. Additional support was provided by the Howard Hughes Medical Institute, with which P.W.S. is an investigator and B.J.H. and B.P.G. were associates. J.L. was supported by a U.S.H.S. training grant. B.P.G. was a postdoctoral fellow of the Human Frontier Science Foundation. N.M. was a fellow of the California Breast Cancer Research Foundation. Some strains were provided by the Caenorhabditis Genetics Center.Attached Files
Published - GEN17431315.pdf
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Additional details
- PMCID
- PMC1667086
- Eprint ID
- 95472
- Resolver ID
- CaltechAUTHORS:20190514-090058420
- NIH
- HD23690
- Canada Research Chairs Program
- McMaster University
- NIH
- R01 GM073184
- Howard Hughes Medical Institute (HHMI)
- Human Frontier Science Foundation
- California Breast Cancer Research Foundation
- Created
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2019-05-14Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field