Gene Symbol: daf-12
Description: Nuclear hormone receptor family member daf-12
Alias: Nuclear hormone receptor family member daf-12
Species: Caenorhabditis elegans
Products:     daf-12

Top Publications

  1. Gill M, Held J, Fisher A, Gibson B, Lithgow G. Lipophilic regulator of a developmental switch in Caenorhabditis elegans. Aging Cell. 2004;3:413-21 pubmed
    ..We propose that the dauer rescuing activity is a hormone synthesized by DAF-9 that acts through DAF-12. ..
  2. Vowels J, Thomas J. Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis elegans. Genetics. 1994;138:303-16 pubmed
    ..We propose that daf-11 and daf-21 mediate sensory transduction for both volatile and non-volatile compounds in specific amphid neurons. ..
  3. Ludewig A, Kober Eisermann C, Weitzel C, Bethke A, Neubert K, Gerisch B, et al. A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging. Genes Dev. 2004;18:2120-33 pubmed
    ..We propose that the DIN-1S/DAF-12 complex serves as a molecular switch that implements slow life history alternatives in response to diminished hormonal signals. ..
  4. Mahanti P, Bose N, Bethke A, Judkins J, Wollam J, Dumas K, et al. Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor, regulating C. elegans development and lifespan. Cell Metab. 2014;19:73-83 pubmed publisher
    ..Our results demonstrate the advantages of comparative metabolomics over traditional candidate-based approaches and provide a blueprint for the identification of ligands for other C. elegans and mammalian NHRs. ..
  5. Hammell C, Karp X, Ambros V. A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2009;106:18668-73 pubmed publisher
    ..We propose that this feedback loop functions to ensure robustness of cell fate decisions and to coordinate cell fate with developmental arrest. ..
  6. Larsen P, Albert P, Riddle D. Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics. 1995;139:1567-83 pubmed
    ..This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. ..
  7. Antebi A, Yeh W, Tait D, Hedgecock E, Riddle D. daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev. 2000;14:1512-27 pubmed
    ..In the adult, expression persists in nervous system and somatic gonad, two tissues that regulate adult longevity. We propose that DAF-12 integrates hormonal signals in cellular targets to coordinate major life history traits. ..
  8. Hochbaum D, Zhang Y, Stuckenholz C, Labhart P, Alexiadis V, Martin R, et al. DAF-12 regulates a connected network of genes to ensure robust developmental decisions. PLoS Genet. 2011;7:e1002179 pubmed publisher
    ..Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions. ..
  9. Motola D, Cummins C, Rottiers V, Sharma K, Li T, Li Y, et al. Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans. Cell. 2006;124:1209-23 pubmed

More Information


  1. Bethke A, Fielenbach N, Wang Z, Mangelsdorf D, Antebi A. Nuclear hormone receptor regulation of microRNAs controls developmental progression. Science. 2009;324:95-8 pubmed publisher
    ..These findings identify microRNAs as components of a hormone-coupled molecular switch that shuts off earlier developmental programs to allow for later ones. ..
  2. Ao W, Gaudet J, Kent W, Muttumu S, Mango S. Environmentally induced foregut remodeling by PHA-4/FoxA and DAF-12/NHR. Science. 2004;305:1743-6 pubmed
    ..Our combination of bioinformatics and in vivo analysis has provided a powerful means for genome-wide investigation of transcriptional control. ..
  3. Shen Y, Wollam J, Magner D, Karalay O, Antebi A. A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science. 2012;338:1472-6 pubmed publisher
    ..Our studies suggest that metazoan life span is coupled to the gonad through elements of a developmental timer. ..
  4. Wang M, O Rourke E, Ruvkun G. Fat metabolism links germline stem cells and longevity in C. elegans. Science. 2008;322:957-60 pubmed publisher
    ..This lipase is a key factor in the lipid hydrolysis and increased longevity that are induced by decreased insulin signaling. These results suggest a link between C. elegans fat metabolism and longevity. ..
  5. Fisher A, Lithgow G. The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis elegans lifespan and regulates genes repressed in multiple long-lived worms. Aging Cell. 2006;5:127-38 pubmed
    ..Our results point to daf-12 modulating aging and stress responses in part through the repression of specific genes, and emphasize the role that the repression of genes that curtail maximal lifespan plays in lifespan determination. ..
  6. Dowell P, Otto T, Adi S, Lane M. Convergence of peroxisome proliferator-activated receptor gamma and Foxo1 signaling pathways. J Biol Chem. 2003;278:45485-91 pubmed
    ..A more general convergence of nuclear hormone receptor and forkhead factor pathways may be important for multiple biological processes and this convergence may be evolutionarily conserved. ..
  7. Vowels J, Thomas J. Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans. Genetics. 1992;130:105-23 pubmed
    ..These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation, while the other Daf-c genes play roles downstream of the chemosensory step. ..
  8. Fitzenberger E, Deusing D, Marx C, Boll M, Lüersen K, Wenzel U. The polyphenol quercetin protects the mev-1 mutant of Caenorhabditis elegans from glucose-induced reduction of survival under heat-stress depending on SIR-2.1, DAF-12, and proteasomal activity. Mol Nutr Food Res. 2014;58:984-94 pubmed publisher
    ..SIR-2.1, DAF-12, and MDT-15 were identified as targets that activate unfolded protein response and proteasomal degradation to limit the accumulation of functionally restricted proteins. ..
  9. McCulloch D, Gems D. Sex-specific effects of the DAF-12 steroid receptor on aging in Caenorhabditis elegans. Ann N Y Acad Sci. 2007;1119:253-9 pubmed
    ..These results could imply that in C. elegans, as in mammals, sex differences in steroid endocrinology contribute to sex differences in aging. ..
  10. Kaplan R, Chen Y, Moore B, Jordan J, Maxwell C, Schindler A, et al. dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest. PLoS Genet. 2015;11:e1005731 pubmed publisher
    ..Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development. ..
  11. Liu F, He C, Luo L, Zou Q, Zhao Y, Saini R, et al. Nuclear hormone receptor regulation of microRNAs controls innate immune responses in C. elegans. PLoS Pathog. 2013;9:e1003545 pubmed publisher
    ..These findings identify nuclear hormone receptors as components of innate immunity that crosstalk with the p38/PMK-1 MAP kinase pathway. ..
  12. Nakamura S, Karalay Ã, Jäger P, Horikawa M, Klein C, Nakamura K, et al. Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals. Nat Commun. 2016;7:10944 pubmed publisher
    ..These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. ..
  13. Tennessen J, Opperman K, Rougvie A. The C. elegans developmental timing protein LIN-42 regulates diapause in response to environmental cues. Development. 2010;137:3501-11 pubmed publisher
  14. Deusing D, Beyrer M, Fitzenberger E, Wenzel U. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12. Biochem Biophys Res Commun. 2015;460:747-52 pubmed publisher
    ..elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. ..
  15. Kleemann G, Jia L, Emmons S. Regulation of Caenorhabditis elegans male mate searching behavior by the nuclear receptor DAF-12. Genetics. 2008;180:2111-22 pubmed publisher
    ..As it does in other pathways in which it functions, in regulation of male mate searching behavior DAF-12 acts at a choice point between alternatives favoring reproduction (mate searching) vs. survival (remaining on food). ..
  16. Colella E, Li S, Roy R. Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva. Genetics. 2016;203:1763-76 pubmed publisher
  17. Yunger E, Safra M, Levi Ferber M, Haviv Chesner A, Henis Korenblit S. Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7. PLoS Genet. 2017;13:e1006577 pubmed publisher
  18. Lee J, Kim K, Lee J, Paik Y. Regulation of Dauer formation by O-GlcNAcylation in Caenorhabditis elegans. J Biol Chem. 2010;285:2930-9 pubmed publisher
    ..Analysis of these candidate O-GlcNAcylated proteins suggests that O-GlcNAcylation may regulate cytoskeleton modifications and protein turnover during dauer formation. ..
  19. Fischer M, Fitzenberger E, Kull R, Boll M, Wenzel U. The zinc matrix metalloproteinase ZMP-2 increases survival of Caenorhabditis elegans through interference with lipoprotein absorption. Genes Nutr. 2014;9:414 pubmed publisher
    ..elegans. Those effects are mediated by the transport of oxidized cholesterol adducts which then trigger the inhibition of DAF-9 and DAF-12 through the activation of DAF-16. ..
  20. Golden J, Riddle D. A pheromone-induced developmental switch in Caenorhabditis elegans: Temperature-sensitive mutants reveal a wild-type temperature-dependent process. Proc Natl Acad Sci U S A. 1984;81:819-23 pubmed
    ..These mutations appear to indirectly result in a ts phenotype by enhancing the expression of a wild-type ts developmental process. ..
  21. Wang Z, Stoltzfus J, You Y, Ranjit N, Tang H, Xie Y, et al. The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes. PLoS Genet. 2015;11:e1005027 pubmed publisher
    ..Our study provides a molecular understanding for metabolic adaptation of nematodes to their environment, and suggests a new therapeutic strategy for treating parasitic diseases. ..
  22. Ludewig A, Gimond C, Judkins J, Thornton S, Pulido D, Micikas R, et al. Larval crowding accelerates C. elegans development and reduces lifespan. PLoS Genet. 2017;13:e1006717 pubmed publisher
    ..Our results demonstrate how inter-organismal signaling during development regulates reproductive maturation and longevity. ..
  23. Jensen V, Bialas N, Bishop Hurley S, Molday L, Kida K, Nguyen P, et al. Localization of a guanylyl cyclase to chemosensory cilia requires the novel ciliary MYND domain protein DAF-25. PLoS Genet. 2010;6:e1001199 pubmed publisher
    ..In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle. ..
  24. Yamawaki T, Berman J, Suchanek Kavipurapu M, McCormick M, Gaglia M, Lee S, et al. The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling. PLoS Biol. 2010;8: pubmed publisher
    ..Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12. ..
  25. Greer E, Perez C, Van Gilst M, Lee B, Ashrafi K. Neural and molecular dissection of a C. elegans sensory circuit that regulates fat and feeding. Cell Metab. 2008;8:118-31 pubmed publisher
    ..Thus, neural perception of adverse environmental conditions can promote fat accumulation without a concomitant increase in feeding rate. ..
  26. Rougvie A. miRNA regulation through ligand occupancy of a nuclear hormone receptor. Sci Signal. 2009;2:pe52 pubmed publisher
    ..Activation versus repression of key developmental miRNAs in Caenorhabditis elegans is directly mediated by ligand occupancy of a nuclear hormone receptor that acts to couple nutrient availability to developmental programs. ..
  27. Dixon S, Alexander M, Chan K, Roy P. Insulin-like signaling negatively regulates muscle arm extension through DAF-12 in Caenorhabditis elegans. Dev Biol. 2008;318:153-61 pubmed publisher
    ..We conclude that supernumerary muscle arms are a novel dauer-specific modification that may facilitate some aspect of dauer behavior. ..
  28. Matyash V, Entchev E, Mende F, Wilsch Bräuninger M, Thiele C, Schmidt A, et al. Sterol-derived hormone(s) controls entry into diapause in Caenorhabditis elegans by consecutive activation of DAF-12 and DAF-16. PLoS Biol. 2004;2:e280 pubmed
    ..This hormonal control of DAF-16 activation is, however, independent of insulin signalling and has no influence on life span. ..
  29. Johnson S, Lin S, Slack F. The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Dev Biol. 2003;259:364-79 pubmed
    ..We speculate that these heterochronic genes regulate let-7 expression through its TRE. ..
  30. Jeong M, Kawasaki I, Shim Y. A circulatory transcriptional regulation among daf-9, daf-12, and daf-16 mediates larval development upon cholesterol starvation in Caenorhabditis elegans. Dev Dyn. 2010;239:1931-40 pubmed publisher
    ..These results altogether suggest that circulatory mutual regulation among daf-9, daf-12, and daf-16 at the expression level mediates cholesterol signal to control larval development upon CS. ..
  31. Shostak Y, Yamamoto K. Overlapping but separable determinants of DNA binding and nuclear localization map to the C-terminal end of the Caenorhabditis elegans DAF-12 DNA binding domain. J Biol Chem. 2005;280:6554-60 pubmed
    ..Thus, DAF-12 dbdC harbors overlapping but separable determinants of DNA binding and nuclear localization in a single small region. ..