Authors: Gerisch B; Weitzel C; Kober-Eisermann C; Rottiers V; Antebi A
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.Keywords: 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
Journal: Developmental cell
Date: Dec. 13, 2001
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Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V, Antebi A (2001) A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Developmental cell 1: 841-51.