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      Functional Genomic Analysis of C. elegans Molting

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      1 , 1 , 1 ,
      PLoS Biology
      Public Library of Science

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          Abstract

          Although the molting cycle is a hallmark of insects and nematodes, neither the endocrine control of molting via size, stage, and nutritional inputs nor the enzymatic mechanism for synthesis and release of the exoskeleton is well understood. Here, we identify endocrine and enzymatic regulators of molting in C. elegans through a genome-wide RNA-interference screen. Products of the 159 genes discovered include annotated transcription factors, secreted peptides, transmembrane proteins, and extracellular matrix enzymes essential for molting. Fusions between several genes and green fluorescent protein show a pulse of expression before each molt in epithelial cells that synthesize the exoskeleton, indicating that the corresponding proteins are made in the correct time and place to regulate molting. We show further that inactivation of particular genes abrogates expression of the green fluorescent protein reporter genes, revealing regulatory networks that might couple the expression of genes essential for molting to endocrine cues. Many molting genes are conserved in parasitic nematodes responsible for human disease, and thus represent attractive targets for pesticide and pharmaceutical development.

          Abstract

          The authors use a genome-wide RNA-interference screen to identify and characterize genes involved in C. elegans molting. They investigate regulatory networks involved in molting, lending important new insights into this complex process.

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          Specific interference by ingested dsRNA.

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            daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.

            A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. Decreased DAF-2 signaling also causes an increase in life-span. Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity.
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              Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.

              Complete genomic sequence is known for two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and it will soon be known for humans. However, biological function has been assigned to only a small proportion of the predicted genes in any animal. Here we have used RNA-mediated interference (RNAi) to target nearly 90% of predicted genes on C. elegans chromosome I by feeding worms with bacteria that express double-stranded RNA. We have assigned function to 13.9% of the genes analysed, increasing the number of sequenced genes with known phenotypes on chromosome I from 70 to 378. Although most genes with sterile or embryonic lethal RNAi phenotypes are involved in basal cell metabolism, many genes giving post-embryonic phenotypes have conserved sequences but unknown function. In addition, conserved genes are significantly more likely to have an RNAi phenotype than are genes with no conservation. We have constructed a reusable library of bacterial clones that will permit unlimited RNAi screens in the future; this should help develop a more complete view of the relationships between the genome, gene function and the environment.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Biol
                pbio
                PLoS Biology
                Public Library of Science (San Francisco, USA )
                1544-9173
                1545-7885
                October 2005
                30 August 2005
                : 3
                : 10
                : e312
                Affiliations
                [1] 1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America, and Genetics Department, Harvard Medical School, Boston, Massachusetts, United States of America
                Utrecht University Netherlands
                Article
                10.1371/journal.pbio.0030312
                1233573
                16122351
                6ebccb08-4cdb-4cc2-8afc-baf6f2c0b9e0
                Copyright: © 2005 Frand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
                History
                : 3 March 2005
                : 7 July 2005
                Categories
                Research Article
                Cell Biology
                Development
                Systems Biology
                Parasitology
                Nematodes
                Caenorhabditis

                Life sciences
                Life sciences

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