Maternal Diet and Insulin-Like Signaling Control Intergenerational Plasticity of Progeny Size and Starvation Resistance.

Jonathan D Hibshman,Anthony Hung,L Ryan Baugh,Kaveh Ashrafi

doi:10.1371/journal.pgen.1006396

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.

Highlights

Developmental physiology can be profoundly influenced by maternal environment
We demonstrate that progeny of Dietary restriction (DR) worms grow faster and are more fertile following extended starvation upon hatching as larvae, as if phenotypic plasticity buffers them from starvation in anticipation of adverse conditions
Food intake is limited by reduced pharyngeal pumping in eat-2 mutant worms, providing a genetic model of DR on solid media with E. coli OP50 as food [33]

Summary

Introduction

Developmental physiology can be profoundly influenced by maternal environment. Mismatch between conditions during early development and later in life is thought to contribute to disease [1,2,3]. Children of malnourished mothers have low birth weight and increased risk of diabetes, obesity, and cardiovascular disease [4,5,6,7]. These effects appear maladaptive, early-life metabolic reprogramming could increase fitness if future conditions are appropriately anticipated. The "thrifty phenotype" is characterized by nutrient rationing and increased fat storage, which in theory is adaptive in poor conditions though posing disease risk in rich conditions [8]. Despite documentation of potentially adaptive maternal effects, molecular mechanisms for intergenerational phenotypic plasticity are generally not understood

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