Structure and expression of daf-12: a nuclear hormone receptor with three isoforms that are involved in development and aging in Caenorhabditis elegans

During Caenorhabditis elegans early larval development environmental condit ions promote a cascade of signaling molecules to direct growth to the repro ductive adult or to arrest development as a dauer larva. Two parallel chemo sensory signal transduction pathways, one of which is transforming growth f actor (TGF)-beta -like, converge on the daf-12 gene to regulate dauer forma tion. A third insulin-like signaling pathway interacts with the daf-12 path way to regulate both dauer formation and adult longevity. To further unders tand the role of daf-12 in these processes, we have molecularly characteriz ed this gene. We establish rescue of the mutant dauer defective phenotype w ith a genomic clone. We show that three transcripts of different lengths, d ue to differential splicing, are made from the daf-12 gene. The deduced pro tein isoforms are similar to both DNA- and ligand-binding domains of nuclea r hormone receptors. The three daf-12 transcripts are produced throughout d evelopment and expression increases during the preparation for and executio n of dauer formation. Analysis of various daf mutant strains suggests that the isoform ratios of daf-12 steady-state mRNA are not changed by reduction of function in the TGF-P and insulin signaling components of the dauer pat hway. The daf-12 promoter directs expression of GFP in the pharynx. daf-12 is a C. elegans nuclear hormone receptor with multiple isoforms, is express ed throughout development in distinct cells, and functions under a variety of environmental conditions. (C) 2000 Elsevier Science B.V. All rights rese rved.