TitleTissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans.
Publication TypeJournal Article
Year of Publication2007
AuthorsMurphy, CT, Lee, S-J, Kenyon, C
JournalProc Natl Acad Sci U S A
Date Published2007 Nov 27
KeywordsAging, Animals, Animals, Genetically Modified, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Endoderm, Feedback, Physiological, Insulin, Intestines, Larva, Longevity, Peptide Hormones, Recombinant Fusion Proteins, Signal Transduction, Superoxide Dismutase, Transcription Factors

How are the rates of aging of different tissues coordinated? In Caenorhabditis elegans, decreasing insulin/IGF-1 signaling extends lifespan by activating the transcription factor DAF-16/FOXO. If DAF-16 levels are experimentally increased in one tissue, such as the intestine, DAF-16 activity in other tissues rises. Here we test the hypothesis that this "FOXO-to-FOXO" signaling occurs via feedback regulation of ins-7 insulin gene expression. We find that DAF-16 regulates ins-7 expression in the intestine, and that preventing this regulation blocks FOXO-to-FOXO signaling from the intestine to other tissues. Our findings show that feedback regulation of insulin gene expression coordinates DAF-16 activity among the tissues, and they establish the intestine, which is the animal's entire endoderm, as an important insulin-signaling center.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.