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