daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C-elegans

The daf-12 gene acts at the convergence of pathways regulating larval diapa use, developmental age, and adult longevity in Caenorhabditis elegans. It e ncodes a nuclear receptor most closely related to two C. elegans receptors, NHR-8 and NHR-48, Drosophila DHR96, and vertebrate vitamin D and pregnane- X receptors. daf-12 has three predicted protein isoforms, two of which cont ain DNA- and ligand-binding domains, and one of which contains the ligand-b inding domain only. Mutations cluster in DNA- and ligand-binding domains, b ut correspond to distinct phenotypic classes. DAF-12 is expressed widely in target tissues from embryo to adult, but is upregulated during midlarval s tages. In the adult, expression persists in nervous system and somatic gona d, two tissues that regulate adult longevity. We propose that DAF-12 integr ates hormonal signals in cellular targets to coordinate major life history traits.