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PLoS One


Title:RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation
Author(s):Jensen VL; Simonsen KT; Lee YH; Park D; Riddle DL;
Address:"Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada"
Journal Title:PLoS One
Year:2010
Volume:20101231
Issue:12
Page Number:e15902 -
DOI: 10.1371/journal.pone.0015902
ISSN/ISBN:1932-6203 (Electronic) 1932-6203 (Linking)
Abstract:"The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366); sdf-9(m708)], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c). Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf) phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85), sdf-9(m708), and the wild-type N2 (at 27 degrees C) were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130) background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production"
Keywords:"Animals Behavior, Animal Caenorhabditis elegans/*genetics/physiology Caenorhabditis elegans Proteins/*genetics Forkhead Transcription Factors Genetic Testing Green Fluorescent Proteins/metabolism Immunity, Innate Insulin/metabolism Insulin Secretion Larva;"
Notes:"MedlineJensen, Victor L Simonsen, Karina T Lee, Yu-Hui Park, Donha Riddle, Donald L eng MOP-79458/Canadian Institutes of Health Research/Canada Research Support, Non-U.S. Gov't 2011/01/07 PLoS One. 2010 Dec 31; 5(12):e15902. doi: 10.1371/journal.pone.0015902"

 
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