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

B Gerisch, C Weitzel, C Kober-Eisermann, V Rottiers… - Developmental cell, 2001 - cell.com
B Gerisch, C Weitzel, C Kober-Eisermann, V Rottiers, A Antebi
Developmental cell, 2001cell.com
During C. elegans development, animals must choose between reproductive growth or
dauer diapause in response to sensory cues. Insulin/IGF-I and TGF-β 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 …
Abstract
During C. elegans development, animals must choose between reproductive growth or dauer diapause in response to sensory cues. Insulin/IGF-I and TGF-β 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.
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