Caenorhabditis elegans OSM-11 signaling regulates SKN-1/Nrf during embryonic development and adult longevity and stress response

Dev Biol. 2015 Apr 1;400(1):118-31. doi: 10.1016/j.ydbio.2015.01.021. Epub 2015 Jan 29.


The Nrf family of transcription factors is critical for stress defense and detoxification. In Caenorhabditis elegans, the Nrf protein ortholog SKN-1 mediates this conserved stress response and promotes longevity. Moreover, SKN-1 is well known for its essential functions during C. elegans embryogenesis. SKN-1 is maternally deployed and initiates a signaling network specifying development of the endoderm and mesoderm. In this study, we identify the conserved Notch ligand OSM-11 as a novel regulator of SKN-1. We find that genetic inactivation of osm-11 re-establishes development of the pharynx and intestine in skn-1 deficient embryos and thereby rescues embryonic lethality associated with loss of skn-1 function. Inactivation of other DSL- and DOS-motif Notch ligands does not prevent skn-1 embryonic lethality. In addition, we show that inactivation of osm-11 in adult worms robustly enhances lifespan and promotes resistance to environmental stress. SKN-1 is required for increased longevity and heat and oxidative stress resistance but not hyperosmotic stress conferred by osm-11. OSM-11 prevents the nuclear accumulation of SKN-1 and represses the transcriptional activation of SKN-1 target genes for cellular detoxification. Our findings indicate that OSM-11 antagonizes SKN-1 during embryonic development and reveal a highly context-specific relationship between OSM-11 and SKN-1 in promoting stress resistance and longevity.

Keywords: Aging; C. elegans; Development; Notch signaling; OSM-11; SKN-1/Nrf; Stress response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Longevity / genetics
  • Longevity / physiology*
  • Oxidative Stress / physiology
  • RNA Interference
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • OSM-11 protein, C elegans
  • Transcription Factors
  • skn-1 protein, C elegans