Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V, Antebi A
Max-Planck Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany.
Dev Cell. 2001 Dec;1(6):841-51. doi: 10.1016/s1534-5807(01)00085-5.
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.
在秀丽隐杆线虫发育过程中，动物必须根据感官线索在生殖生长和 dauer 滞育之间做出选择。胰岛素/IGF-I 和 TGF-β 信号通路汇聚于孤儿核受体 daf-12 以介导这一选择。在此我们表明，daf-9 在这些输入信号的下游起作用，但在 daf-12 的上游。daf-9 和 daf-12 突变体具有相似的幼虫缺陷，并调节胰岛素/IGF-I 和性腺信号，这些信号调节成虫寿命。daf-9 编码一种与脊椎动物类固醇生成羟化酶相关的细胞色素 P450，这表明它可能代谢一种 DAF-12 配体。固醇可能是 daf-9 的底物和 daf-12 的配体，因为胆固醇剥夺模拟了突变体缺陷。表达 daf-9 的感觉神经元、皮下组织和体细胞性腺细胞确定了潜在的内分泌组织。显然，亲脂性激素影响线虫的代谢、滞育和寿命。
