rnai screen of daf-16foxo target genes in c. elegans links pathogenesis and dauer formationrnai屏幕daf-16foxo目标基因的秀丽隐杆线虫发病机理和多尔形成的链接.pdfVIP

RNAi Screen of DAF-16/FOXO Target Genes in C. elegans Links Pathogenesis and Dauer Formation 1,2 3 2 2 1,2 Victor L. Jensen , Karina T. Simonsen , Yu-Hui Lee , Donha Park , Donald L. Riddle * 1 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, 2 Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada, 3 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark 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 27uC) were all enhanced by exposure to pathogenic bacteria, while not e