title: Metabolite induction of Caenorhabditis elegans dauer larvae arises via transport in the pharynx.
abstract: Caenorhabditis elegans sense natural chemicals in their environment and use them as cues to regulate their development. This investigation probes the mechanism of sensory trafficking by evaluating the processing of fluorescent derivatives of natural products in C. elegans. Fluorescent analogs of daumone, an ascaroside, and apigenin were prepared by total synthesis and evaluated for their ability to induce entry into a nonaging dauer state. Fluorescent imaging detailed the uptake and localization of every labeled compound at each stage of the C. elegans life cycle. Comparative analyses against natural products that did not induce dauer indicated that dauer-triggering natural products accumulated in the cuticle of the pharnyx. Subsequent transport of these molecules to amphid neurons signaled entry into the dauer state. These studies provide cogent evidence supporting the roles of the glycosylated fatty acid daumone and related ascarosides and the ubiquitous plant flavone apigenin as chemical cues regulating C. elegans development.
authors: Howard Hughes Medical Institute, Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors: Thomas J
authors: TJ
authors: Baiga
authors: Haibing
authors: H
authors: Guo
authors: Yalan
authors: Y
authors: Xing
authors: George A
authors: GA
authors: O'Doherty
authors: Andrew
authors: A
authors: Dillin
authors: Michael B
authors: MB
authors: Austin
authors: Joseph P
authors: JP
authors: Noel
authors: James J
authors: JJ
authors: La Clair
mesh_terms: D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D015394:Molecular Structure; D010614:Pharynx / Q000187:drug effects / Q000378:metabolism*; D010675:Pheromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D005456:Fluorescent Dyes; D010675:Pheromones; C496586:daumone, C elegans