RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation.
RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation.
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DOI：
10.1371/journal.pone.0015902
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发表时间：
2010-12-31
期刊：
影响因子：
3.7
通讯作者：
Riddle DL
中科院分区：
文献类型：
--
作者：
Jensen VL;Simonsen KT;Lee YH;Park D;Riddle DL
β-16/FOXO转录因子是胰岛素/IGF 1 R信号通路控制C.线虫幼虫的发育和衰老。为了鉴定影响dauer形成的新的下游基因，我们使用RNAi筛选先前鉴定为受miR-16调控的候选基因。我们使用了敏化的遗传背景[eri-1（mg366）; sdf-9（m708）]，其增强了RNAi效率和组成型dauer形成（Daf-c）。在筛选的513个RNAi克隆中，21个显示合成的Daf-c（SynDaf）表型与sdf-9。这些基因之一，srh-100，以前被确定为SynDaf，但二十以前没有与dauer形成。已知后两个基因lys-1和cpr-1参与先天免疫，预计还有六个基因也会参与先天免疫，这表明免疫反应可能有助于dauer决定。事实上，我们发现，这些基因中的两个，lys-1和clc-1，是正常的耐金黄色葡萄球菌所必需的。预测CLC-1在上皮粘附中起作用。由daf-8（m85）、sdf-9（m708）和野生型N2（在27°C下）表现出的Dauer形成都通过暴露于病原性细菌而增强，而在daf-22（m130）背景下不增强。我们的结论是，适当的病原体抗性所需的基因敲低增加了病原体感染，导致我们的筛选中dauer形成增加。我们建议，dauer幼虫形成是一种行为反应介导的病原体增加dauer信息素的生产。
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.
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