Abstract
Environmental conditions experienced during animal development are thought to have sustained impact on maturation and adult lifespan. Here we show that in the model organism C. elegans developmental rate and adult lifespan depend on larval population density, and that this effect is mediated by excreted small molecules. By using the time point of first egg laying as a marker for full maturity, we found that wildtype hermaphrodites raised under high density conditions developed significantly faster than animals raised in isolation. Population density-dependent acceleration of development (Pdda) was dramatically enhanced in fatty acid β-oxidation mutants that are defective in the biosynthesis of ascarosides, small-molecule signals that induce developmental diapause. In contrast, Pdda is abolished by synthetic ascarosides and steroidal ligands of the nuclear hormone receptor DAF-12. We show that neither ascarosides nor any known steroid hormones are required for Pdda and that another chemical signal mediates this phenotype, in part via the nuclear hormone receptor NHR-8. Our results demonstrate that C. elegans development is regulated by a push-pull mechanism, based on two antagonistic chemical signals: chemosensation of ascarosides slows down development, whereas population-density dependent accumulation of a different chemical signal accelerates development. We further show that the effects of high larval population density persist through adulthood, as C. elegans larvae raised at high densities exhibit significantly reduced adult lifespan and respond differently to exogenous chemical signals compared to larvae raised at low densities, independent of density during adulthood. Our results demonstrate how inter-organismal signaling during development regulates reproductive maturation and longevity.
Highlights
Sensing environmental conditions is of central importance for organismal development and survival and has been recognized as a major driver of adaptive evolution [1,2]
We found that C. elegans development is regulated by a pull-push mechanism, based on at least two different types of pheromonelike signals: the developmental acceleration signal we first describe in this manuscript, and its antagonist, the dauer pheromone, whose chemical make-up has gradually emerged over the past 10 years
We found that the total number of progeny on the first day of egg laying was increased in HD worms (S2 Fig); total numbers of eggs laid were similar for ISO and HD worms (S2 Fig)
Summary
Sensing environmental conditions is of central importance for organismal development and survival and has been recognized as a major driver of adaptive evolution [1,2]. The nematode Caenorhabditis elegans is a useful model for studying the effects of complex environmental inputs on development and lifespan [3,4], and C. elegans has become one of the most important models for studying conserved mechanisms of aging. High population density under conditions of dietary restriction triggers arrest of development as dauer larvae, a long-lived, highly stress resistant alternate larval stage that can persist under adverse environmental conditions for many months [4]. The dauer-inducing population density signal was shown to consist of a synergistic mixture of small molecules, the ascarosides [5,6,7]. Perception of dauer-inducing ascarosides downregulates insulin, cGMP and TGFβ signaling, which in turn downregulates expression of enzymes involved in the biosynthesis of steroid hormones called dafachronic acids (DAs), the endogenous ligands of the nuclear receptor DAF12, a homolog of vertebrate vitamin D and liver-X receptors [8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
