RRC ID 4180
Author Murphy CT, Lee SJ, Kenyon C.
Title Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract 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.
Volume 104(48)
Pages 19046-50
Published 2007-11-27
DOI 10.1073/pnas.0709613104
PII 0709613104
PMID 18025456
PMC PMC2141905
MeSH Aging / genetics* Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Endoderm / physiology* Feedback, Physiological / physiology* Forkhead Transcription Factors Insulin / physiology* Intestines / physiology* Larva Longevity / genetics Peptide Hormones / genetics Peptide Hormones / physiology* Recombinant Fusion Proteins / physiology Signal Transduction Superoxide Dismutase / biosynthesis Superoxide Dismutase / genetics Transcription Factors / genetics Transcription Factors / physiology*
IF 9.504
Times Cited 77
C.elegans tm1907 tm2001 tm1849 tm1723