Transcriptome and phenotype-based epistasis analysis in Caenorhabditis elegans reveal daf-16/FoxO-dependent and independent effects of daf-2/InsR in L1 arrest and recovery

Reduced insulin/IGF signaling (IIS) in C. elegans increases starvation resistance in daf-16/FoxO-dependent fashion, but it is unclear whether the effects of reduced IIS are entirely dependent on daf-16/FoxO or if another effector(s) of IIS may be involved. We used RNA sequencing (RNA-seq) and phenotypic analysis of L1 starvation resistance to assess epistasis between daf-2/InsR and daf-16/FoxO. Essentially all differential gene expression caused by disruption of daf-2/InsR during starvation is daf-16-dependent. The effects of daf-2/InsR on starvation survival also appear entirely dependent on daf-16/FoxO, and the effect of daf-2/InsR on growth following starvation is largely daf-16-dependent. However, we also show daf-16-independent effects on growth and reproduction following recovery from starvation. These results support the conclusion that the effects of reduced IIS during L1 starvation are essentially daf-16/FoxO-dependent, but that reduced IIS engages one or more additional effectors during development following starvation. Overall design: RNA-seq of fed and starved (12 hrs after hatch) wild type (N2), as well as starved daf-2(e1370), daf-16(mgDf47), and daf-16(mgDf47); daf-2(e1370) mutants