In response to starvation during the first larval (L1) stage, Caenorhabditis elegans may undergo developmental arrest to enter a state of diapause. Initiation and maintenance of starvation-induced diapause are mediated by signaling through the insulin pathway and can be reversed by food. Kniazeva et al. report that L1 arrest can also be induced by deficiency of the monomethyl branched-chain fatty acid C17ISO, a leucine catabolite. Animals without C17ISO were generated through RNA interference (RNAi) with edo-5, which encodes an elongation factor required for C17ISO biosynthesis. C17ISO-deficient animals entered an L1 diapause that was phenotypically similar to that induced by starvation and that could be reversed by dietary supplementation with C17ISO. Starvation-induced and C17ISO deficiency-induced diapause states were initiated and maintained independently: C17ISO supplements did not prevent or reverse starvation-induced arrest, and food did not prevent or reverse C17ISO deficiency-induced arrest. Genetic interaction experiments indicated that C17ISO deficiency-induced arrest, unlike starvation-induced arrest, did not require signaling through the insulin receptor DAF-2. Loss-of-function mutations in genes encoding daf-16, which encodes the FOXO transcription factor repressed by DAF-2, or daf-18, which encodes the DAF-2 antagonist Pten, did not suppress C17ISO deficiency-induced developmental arrest. Although not mediated by the same signaling pathway, both starvation-induced and C17ISO deficiency-induced arrest were associated with decreased expression of cki-1, which encodes a cyclin-dependent kinase that promotes cell cycle exit. Genetic interaction experiments coupled with reporter assays indicated that C17ISO biosynthesis was regulated by both lipid metabolism and dietary protein uptake. It is not surprising that metabolic information and nutritional information are integrated to influence developmental decisions, but it is unexpected that a type of metabolism- or nutrient-induced developmental arrest in C. elegans does not depend on insulin signaling.
M. Kniazeva, T. Euler, M. Han, A branched-chain fatty acid is involved in post-embryonic growth control in parallel to the insulin receptor pathway and its biosynthesis is feedback-regulated in C. elegans. Genes & Dev. 22, 2102-2110 (2008). [Abstract] [Full Text]