A circulatory transcriptional regulation among daf‐9, daf‐12 , and daf‐16 mediates larval development upon cholesterol starvation in Caenorhabditis elegans †

C. elegans shows dauer-like larvae formation upon cholesterol starvation (CS), but the genetic epistasis among abnormal dauer formation (daf) genes during the process remains unclear. To clarify the genetic interactions among daf-9, daf-12, and daf-16 in this process, mRNA levels of these genes upon CS were measured. CS increased the mRNA levels of daf-9, daf-12, and daf-16. CS also induced DAF-16 nuclear localization, which was positively and negatively regulated by DAF-12 and DAF-9 activities, respectively. Activated DAF-16, a FOXO transcription factor, enhanced daf-12 but suppressed daf-9 expression, whereas DAF-9 inhibited daf-12 expression. Concomitantly, CS-induced larval arrest was regulated positively by DAF-12 and DAF-16, but negatively by DAF-9. The larval arrest in daf-9 mutant was suppressed by daf-12 RNAi, placing DAF-12 downstream of DAF-9. These results altogether suggest that circulatory mutual regulation among daf-9, daf-12, and daf-16 at the expression level mediates cholesterol signal to control larval development upon CS.