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Published online on November 19, 2007, 10.1073/pnas.0709613104
PNAS | November 27, 2007 | vol. 104 | no. 48 | 19046-19050


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BIOLOGICAL SCIENCES / GENETICS
Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans

Coleen T. Murphy*, Seung-Jae Lee, and Cynthia Kenyon{dagger}

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2200

Contributed by Cynthia Kenyon, October 11, 2007 (received for review January 24, 2007)

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.

aging | DAF-2 | DAF-16 | FOXO

Author contributions: C.T.M. and S.-J.L. contributed equally to this work; C.T.M., S.-J.L., and C.K. designed research; C.T.M. and S.-J.L. performed experiments and contributed new analytical tools; and C.T.M., S.-J.L., and C.K. analyzed data and wrote the paper.

*Present address: Lewis–Sigler Institute of Integrative Genomics and Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0709613104/DC1.

{dagger}To whom correspondence should be addressed. E-mail: ckenyon{at}biochem.ucsf.edu

© 2007 by The National Academy of Sciences of the USA


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