After hatching from eggs when enviromental conditions are favorable, C. The best studied of these pathways exists in the free-living nematode Caenorhabditis elegans (C. The evolutionary success of nematodes is derived from their ability to adapt different developmental pathways depending on environmental conditions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. DJM is an investigator of the Howard Hughes Medical Institute. Welch Foundation Grants I-1275 (DJM) and I-1558 (SAK). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: This work was supported by the Howard Hughes Medical Institute (DJM), the National Institutes of Health U24-DK098908-02 (DJM, SAK), R01-AI050668 and R21-AI105856 (JBL), the Australian National Health and Medical Research Council, Training fellowship APP 1016858 (NR), Virginia Commonwealth University School of Medicine (YY), and Robert A. Received: AugAccepted: JanuPublished: March 16, 2015Ĭopyright: © 2015 Wang et al. (2015) The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes. These findings elucidate a molecular mechanism for how nematodes govern their energy needs in response to the environment, and provide a potential new strategy for treating nematode parasitic diseases.Ĭitation: Wang Z, Stoltzfus J, You Y-j, Ranjit N, Tang H, Xie Y, et al. Through analogous studies in the incurable human parasite, Strongyloides stercoralis, we demonstrate that this pathway is conserved and that blocking it compromises the viability of the parasites. Given that dafachronic acids are produced only in well-fed worms, we conclude that DAF-12 functions as an environmental sensor that coordinately governs energy homeostasis. Through gene expression analysis, we show that DAF-12 regulates a network of genes involved in energy homeostasis and lipid metabolism.
By responding to its endogenous ligands, called dafachronic acids, DAF-12 induces oxidation of lipids to produce the energy necessary to support growth and reproduction and likewise, in the absence of dafachronic acids, DAF-12 prevents activation of this pathway. In this study, we report that in a nutrient rich environment the free-living nematode, Caenorhabditis elegans, induces an energy-generating metabolic pathway to govern its reproductive growth by activating the nuclear receptor, DAF-12. Animals adjust their internal biological processes in response to their environments.
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