title: Maternal Diet and Insulin-Like Signaling Control Intergenerational Plasticity of Progeny Size and Starvation Resistance.
abstract: Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny. Nutrient availability is assessed in late larvae and young adults, rather than affecting a set point in young larvae, and maternal age independently affects progeny size. Reduced signaling through the insulin-like receptor daf-2/InsR in the maternal soma causes constitutively large progeny, and its effector daf-16/FoxO is required for this effect. nhr-49/Hnf4, pha-4/FoxA, and skn-1/Nrf also regulate progeny-size plasticity. Genetic analysis suggests that insulin-like signaling controls progeny size in part through regulation of nhr-49/Hnf4, and that pha-4/FoxA and skn-1/Nrf function in parallel to insulin-like signaling and nhr-49/Hnf4. Furthermore, progeny of DR worms are buffered from adverse consequences of early-larval starvation, growing faster and producing more offspring than progeny of worms fed ad libitum. These results suggest a fitness advantage when mothers and their progeny experience nutrient stress, compared to an environmental mismatch where only progeny are stressed. This work reveals maternal provisioning as an organismal response to DR, demonstrates potentially adaptive intergenerational phenotypic plasticity, and identifies conserved pathways mediating these effects.
authors: Department of Biology, Duke University, Durham, North Carolina, United States of America.|University Program in Genetics and Genomics, Duke University, Durham, North Carolina, United States of America.
authors: Jonathan D
authors: http://orcid.org/0000-0001-7324-9382
authors: JD
authors: Hibshman
authors: Department of Biology, Duke University, Durham, North Carolina, United States of America.
authors: Anthony
authors: http://orcid.org/0000-0002-4725-0635
authors: A
authors: Hung
authors: Department of Biology, Duke University, Durham, North Carolina, United States of America.|University Program in Genetics and Genomics, Duke University, Durham, North Carolina, United States of America.
authors: L Ryan
authors: http://orcid.org/0000-0003-2148-5492
authors: LR
authors: Baugh
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004032:Diet; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008136:Longevity / Q000235:genetics; D000072741:Maternal Inheritance / Q000235:genetics*; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013217:Starvation / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C505159:NHR-49 protein, C elegans; C113277:Pha-4 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C073702:skn-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin