title: A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span.
abstract: 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.
authors.affiliation: Max-Planck Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Gerisch
authors.forename: C
authors.initials: C
authors.lastname: Weitzel
authors.forename: C
authors.initials: C
authors.lastname: Kober-Eisermann
authors.forename: V
authors.initials: V
authors.lastname: Rottiers
authors.forename: A
authors.initials: A
authors.lastname: Antebi
mesh_terms: 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
chemical_list: 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