Developmental Cell 1: 841-851 (2001)

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

Birgit Gerisch, Cindy Weitzel, Corinna Kober-Eisermann, Veerle Rottiers, and Adam Antebi

Max-Planck Institut fur Molekulare Genetik Ihnestr. 73 D-14195 Berlin Germany.

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.