A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span.
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.
Gerisch
B
B
Max-Planck Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany.
Weitzel
C
C
Kober-Eisermann
C
C
Rottiers
V
V
Antebi
A
A
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D017930:Genes, Reporter; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007814:Larva / Q000033:anatomy & histology / Q000502:physiology*; D008136:Longevity; D008954:Models, Biological; D010641:Phenotype; D010802:Phylogeny; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol