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    Pheromones and Nutritional Signals Regulate the Developmental Reliance on let-7 Family MicroRNAs in C. elegans

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    Authors
    Ilbay, Orkan
    Ambros, Victor R.
    UMass Chan Affiliations
    Graduate School of Biomedical Sciences
    Program in Molecular Medicine
    Document Type
    Journal Article
    Publication Date
    2019-06-03
    Keywords
    ascarosides
    dauer larva
    developmental robustness
    endocrine signaling
    heterochronic genes
    let-7
    microRNAs
    pheromones
    reprogramming
    stem cell
    Developmental Biology
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    Link to Full Text
    https://doi.org/10.1016/j.cub.2019.04.034
    Abstract
    Adverse environmental conditions can affect rates of animal developmental progression and lead to temporary developmental quiescence (diapause), exemplified by the dauer larva stage of the nematode Caenorhabditis elegans (C. elegans). Remarkably, patterns of cell division and temporal cell-fate progression in C. elegans larvae are not affected by changes in developmental trajectory. However, the underlying physiological and gene regulatory mechanisms that ensure robust developmental patterning despite substantial plasticity in developmental progression are largely unknown. Here, we report that diapause-inducing pheromones correct heterochronic developmental cell lineage defects caused by insufficient expression of let-7 family microRNAs in C. elegans. Moreover, two conserved endocrine signaling pathways, DAF-7/TGF-beta and DAF-2/Insulin, that confer on the larva diapause and non-diapause alternative developmental trajectories interact with the nuclear hormone receptor, DAF-12, to initiate and regulate a rewiring of the genetic circuitry controlling temporal cell fates. This rewiring includes engagement of certain heterochronic genes, lin-46, lin-4, and nhl-2, that are previously associated with an altered genetic program in post-diapause animals, in combination with a novel ligand-independent DAF-12 activity, to downregulate the critical let-7 family target Hunchback-like-1 (HBL-1). Our results show how pheromone or endocrine signaling pathways can coordinately regulate both developmental progression and cell-fate transitions in C. elegans larvae under stress so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory.
    Source

    Curr Biol. 2019 Jun 3;29(11):1735-1745.e4. doi: 10.1016/j.cub.2019.04.034. Epub 2019 May 16. Link to article on publisher's site

    DOI
    10.1016/j.cub.2019.04.034
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/44503
    PubMed ID
    31104929
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cub.2019.04.034
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    UMass Chan Faculty and Researcher Publications

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