The Caenorhabditis elegans Synthetic Multivulva Genes Prevent Ras Pathway Activation by Tightly Repressing Global Ectopic Expression of lin-3 EGF
Name
Saffer-2011-The Caenorhabditis e.pdf
Size
3.17 MB
Format
Adobe PDF
Checksum (MD5)
6c869e22772fe2f9d753a12b1c28b499
Author(s)
Saffer, Adam M.
Kim, Dong hyun
van Oudenaarden, Alexander
Horvitz, Howard Robert
Date Issued
December 2011
Journal
PLoS Genetics
Publisher
Public Library of Science
Citation
Saffer, Adam M. et al. “The Caenorhabditis Elegans Synthetic Multivulva Genes Prevent Ras Pathway Activation by Tightly Repressing Global Ectopic Expression of Lin-3 EGF.” Ed. Andrew D. Chisholm. PLoS Genetics 7.12 (2011): e1002418. Web. 23 Feb. 2012.
Version
Final published version
Abstract
The Caenorhabditis elegans class A and B synthetic multivulva (synMuv) genes redundantly antagonize an EGF/Ras pathway to prevent ectopic vulval induction. We identify a class A synMuv mutation in the promoter of the lin-3 EGF gene, establishing that lin-3 is the key biological target of the class A synMuv genes in vulval development and that the repressive activities of the class A and B synMuv pathways are integrated at the level of lin-3 expression. Using FISH with single mRNA molecule resolution, we find that lin-3 EGF expression is tightly restricted to only a few tissues in wild-type animals, including the germline. In synMuv double mutants, lin-3 EGF is ectopically expressed at low levels throughout the animal. Our findings reveal that the widespread ectopic expression of a growth factor mRNA at concentrations much lower than that in the normal domain of expression can abnormally activate the Ras pathway and alter cell fates. These results suggest hypotheses for the mechanistic basis of the functional redundancy between the tumor-suppressor-like class A and B synMuv genes: the class A synMuv genes either directly or indirectly specifically repress ectopic lin-3 expression; while the class B synMuv genes might function similarly, but alternatively might act to repress lin-3 as a consequence of their role in preventing cells from adopting a germline-like fate. Analogous genes in mammals might function as tumor suppressors by preventing broad ectopic expression of EGF-like ligands.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pgen.1002418
