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Genes & Dev. 22 (15): 2102-2110

Copyright © 2008 by Cold Spring Harbor Laboratory Press.

A branched-chain fatty acid is involved in post-embryonic growth control in parallel to the insulin receptor pathway and its biosynthesis is feedback-regulated in C. elegans

Marina Kniazeva2, Tanya Euler,, and Min Han1

Howard Hughes Medical Institute and the Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA

Abstract: Growth and development of multicellular organisms are controlled by signaling systems that sense nutrition availability and metabolic status. We report a novel and surprising factor in Caenorhabditis elegans development, the monomethyl branched-chain fatty acid C17ISO, a product of leucine catabolism. We show here that C17ISO is an essential constituent in a novel mechanism that acts in parallel with the food-sensing DAF-2 (insulin receptor)/DAF-16 (FOXO) signaling pathway to promote post-embryonic development, and that the two pathways converge on a common target repressing cell cycle. We show that C17ISO homeostasis is regulated by a SREBP-1c-mediated feedback mechanism that is different from the SREBP-1c-mediated regulation of common fatty acid biosynthesis, as well as by peptide uptake and transport. Our data suggest that C17ISO may act as a chemical/nutritional factor in a mechanism that regulates post-embryonic development in response to the metabolic state of the organism.

Key Words: C17ISO • daf-2 • FOXO • elo-5 • SREBP • cki-1

Received for publication May 6, 2008. Accepted for publication June 6, 2008.

1 Corresponding authors.

E-MAIL mhan{at}colorado.edu; FAX (303) 735-0175.

2 E-MAIL marinak{at}colorado.edu; FAX (303) 735-0175.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1692008.

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