The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators. Author Rachel Kaletsky, Vanisha Lakhina, Rachel Arey, April Williams, Jessica Landis, Jasmine Ashraf, Coleen Murphy Publication Year 2016 Type Journal Article Abstract Insulin/insulin-like growth factor signalling (IIS) is a critical regulator of an organism's most important biological decisions from growth, development, and metabolism to reproduction and longevity. It primarily does so through the activity of the DAF-16 transcription factor (forkhead box O (FOXO) homologue), whose global targets were identified in Caenorhabditis elegans using whole-worm transcriptional analyses more than a decade ago. IIS and FOXO also regulate important neuronal and adult behavioural phenotypes, such as the maintenance of memory and axon regeneration with age, in both mammals and C. elegans, but the neuron-specific IIS/FOXO targets that regulate these functions are still unknown. By isolating adult C. elegans neurons for transcriptional profiling, we identified both the wild-type and IIS/FOXO mutant adult neuronal transcriptomes for the first time. IIS/FOXO neuron-specific targets are distinct from canonical IIS/FOXO-regulated longevity and metabolism targets, and are required for extended memory in IIS daf-2 mutants. The activity of the forkhead transcription factor FKH-9 in neurons is required for the ability of daf-2 mutants to regenerate axons with age, and its activity in non-neuronal tissues is required for the long lifespan of daf-2 mutants. Together, neuron-specific and canonical IIS/FOXO-regulated targets enable the coordinated extension of neuronal activities, metabolism, and longevity under low-insulin signalling conditions. Keywords Animals, Mutation, Signal Transduction, Phenotype, Neurons, Aging, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Insulin, Longevity, Cell Separation, Forkhead Transcription Factors, Axons, Transcriptome, Memory, Mechanotransduction, Cellular, Regeneration, Somatomedins Journal Nature Volume 529 Issue 7584 Pages 92-6 Date Published 01/2016 ISSN Number 1476-4687 DOI 10.1038/nature16483 Alternate Journal Nature PMCID PMC4708089 PMID 26675724 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML