A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span

Dev Cell. 2001 Dec;1(6):841-51. doi: 10.1016/s1534-5807(01)00085-5.


During C. elegans development, animals must choose between reproductive growth or dauer diapause in response to sensory cues. Insulin/IGF-I and TGF-beta signaling converge on the orphan nuclear receptor daf-12 to mediate this choice. Here we show that daf-9 acts downstream of these inputs but upstream of daf-12. daf-9 and daf-12 mutants have similar larval defects and modulate insulin/IGF-I and gonadal signals that regulate adult life span. daf-9 encodes a cytochrome P450 related to vertebrate steroidogenic hydroxylases, suggesting that it could metabolize a DAF-12 ligand. Sterols may be the daf-9 substrate and daf-12 ligand because cholesterol deprivation phenocopies mutant defects. Sensory neurons, hypodermis, and somatic gonadal cells expressing daf-9 identify potential endocrine tissues. Evidently, lipophilic hormones influence nematode metabolism, diapause, and life span.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / classification
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cholesterol / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Epistasis, Genetic
  • Genes, Reporter
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Larva / anatomy & histology
  • Larva / physiology*
  • Longevity
  • Models, Biological
  • Phenotype
  • Phylogeny
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reproduction / physiology
  • Signal Transduction*
  • Tissue Distribution
  • Transforming Growth Factor beta / metabolism


  • Caenorhabditis elegans Proteins
  • DAF-12 protein, C elegans
  • Insulin
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Transforming Growth Factor beta
  • Insulin-Like Growth Factor I
  • Cytochrome P-450 Enzyme System
  • Cholesterol