dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest
Copyright policy )dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest
Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development.
- Duke University United States
- Department of Biology, Indiana University United States
- DUKE UNIVERSITY
- Department of Biology United States
- University of California, San Francisco United States
571, Embryo, Nonmammalian, Cytoplasmic and Nuclear, Messenger, Embryonic Development, Receptors, Cytoplasmic and Nuclear, QH426-470, 430, Somatomedins, Transforming Growth Factor beta, Receptors, Genetics, Animals, Humans, Insulin, Developmental, RNA, Messenger, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Nonmammalian, Neuropeptides, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, Gene Expression Regulation, Embryo, Starvation, Larva, RNA, Research Article, Signal Transduction
571, Embryo, Nonmammalian, Cytoplasmic and Nuclear, Messenger, Embryonic Development, Receptors, Cytoplasmic and Nuclear, QH426-470, 430, Somatomedins, Transforming Growth Factor beta, Receptors, Genetics, Animals, Humans, Insulin, Developmental, RNA, Messenger, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Nonmammalian, Neuropeptides, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, Gene Expression Regulation, Embryo, Starvation, Larva, RNA, Research Article, Signal Transduction
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