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Vol. 14, No. 12, pp. 1512-1527, June 15, 2000
1 Max-Planck-Institut fuer Molekulare Genetik, Ihnestrasse
73 14195 Berlin, Germany; 2 Molecular Biology Program and
Division of Biological Sciences, University of Missouri, Columbia,
Missouri 65211 USA; 3 Department of Biology, Johns
Hopkins University, Baltimore, Maryland 21218 USA.
The daf-12 gene acts at the convergence of pathways
regulating larval diapause, developmental age, and adult longevity in Caenorhabditis elegans. It encodes 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 contain DNA- and ligand-binding domains, and one of which
contains the ligand-binding domain only. Mutations cluster in DNA- and
ligand-binding domains, but correspond to distinct phenotypic classes.
DAF-12 is expressed widely in target tissues from embryo to adult, but
is upregulated during midlarval stages. In the adult, expression
persists in nervous system and somatic gonad, two tissues that regulate
adult longevity. We propose that DAF-12 integrates hormonal signals in
cellular targets to coordinate major life history traits.
[Key Words: Nuclear receptor; dauer formation; heterochronic gene; aging; diapause; endocrine regulation]
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