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RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation
Victor L Jensen1, Karina T Simonsen, Yu-Hui Lee
1Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
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°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.
Insights
Researchers screened genes affecting dauer formation in C. elegans, identifying novel immune-related genes. Pathogen resistance genes are crucial for dauer larva development, suggesting a link between immunity and this developmental response.
Area of Science:
- Genetics
- Developmental Biology
- Immunology
Background:
- The DAF-16/FOXO transcription factor regulates dauer larva development and aging in C. elegans.
- Identifying novel downstream genes of DAF-16 is crucial for understanding dauer formation.
Purpose of the Study:
- To identify novel genes that regulate dauer formation in C. elegans.
- To investigate the role of innate immunity in dauer development.
Main Methods:
- RNA interference (RNAi) screen in a sensitized genetic background [eri-1(mg366); sdf-9(m708)].
- Screened 513 RNAi clones for synthetic constitutive dauer formation (SynDaf) phenotype with sdf-9.
- Assessed the role of identified genes in pathogen resistance and dauer formation.
Main Results:
- Identified 21 genes with a SynDaf phenotype, 20 of which are novel to dauer formation.
- Two identified genes, lys-1 and cpr-1, are involved in innate immunity.
- Genes required for pathogen resistance (lys-1, clc-1) are essential for normal resistance to Staphylococcus aureus.
- Dauer formation was enhanced by pathogenic bacteria in multiple genetic backgrounds.
Conclusions:
- Innate immune genes play a significant role in dauer larva development.
- Pathogen resistance is linked to dauer formation, suggesting it's a response to infection.
- Dauer larva formation may be a behavioral response to pathogens mediated by dauer pheromone production.
