Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA

Tetsuya Nakamura, Daisuke Saito, Aiko Kawasumi, Kyosuke Shinohara, Yasuko Asai, Katsuyoshi Takaoka, Fenglan Dong, Atsuko Takamatsu, Jose Antonio Belo, Atsushi Mochizuki, Hiroshi Hamada

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Breaking of left-right symmetry in mouse embryos requires fluid flow at the node, but the precise action of the flow has remained unknown. Here we show that the left-right asymmetry of Cerl2 expression around the node, a target of the flow, is determined post-transcriptionally by decay of Cerl2 mRNA in a manner dependent on its 3′ untranslated region. Cerl2 mRNA is absent specifically from the apical region of crown cells on the left side of the node. Preferential decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt-Cerl2 interlinked feedback loops, in which Wnt3 upregulates Wnt3 expression and promotes Cerl2 mRNA decay, whereas Cerl2 promotes Wnt degradation. Mathematical modelling and experimental data suggest that these feedback loops behave as a bistable switch that can amplify in a noise-resistant manner a small bias conferred by fluid flow.

    Original languageEnglish
    Article number2319
    JournalNature Communications
    Volume3
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    RNA Stability
    fluid flow
    Flow of fluids
    Feedback
    Messenger RNA
    decay
    embryos
    3' Untranslated Regions
    Crowns
    mice
    Noise
    Up-Regulation
    Embryonic Structures
    switches
    asymmetry
    degradation
    Switches
    symmetry
    cells
    Degradation

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Chemistry(all)
    • Physics and Astronomy(all)

    Cite this

    Nakamura, T., Saito, D., Kawasumi, A., Shinohara, K., Asai, Y., Takaoka, K., ... Hamada, H. (2012). Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA. Nature Communications, 3, [2319]. https://doi.org/10.1038/ncomms2319

    Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA. / Nakamura, Tetsuya; Saito, Daisuke; Kawasumi, Aiko; Shinohara, Kyosuke; Asai, Yasuko; Takaoka, Katsuyoshi; Dong, Fenglan; Takamatsu, Atsuko; Belo, Jose Antonio; Mochizuki, Atsushi; Hamada, Hiroshi.

    In: Nature Communications, Vol. 3, 2319, 2012.

    Research output: Contribution to journalArticle

    Nakamura, T, Saito, D, Kawasumi, A, Shinohara, K, Asai, Y, Takaoka, K, Dong, F, Takamatsu, A, Belo, JA, Mochizuki, A & Hamada, H 2012, 'Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA', Nature Communications, vol. 3, 2319. https://doi.org/10.1038/ncomms2319
    Nakamura, Tetsuya ; Saito, Daisuke ; Kawasumi, Aiko ; Shinohara, Kyosuke ; Asai, Yasuko ; Takaoka, Katsuyoshi ; Dong, Fenglan ; Takamatsu, Atsuko ; Belo, Jose Antonio ; Mochizuki, Atsushi ; Hamada, Hiroshi. / Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA. In: Nature Communications. 2012 ; Vol. 3.
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    AU - Asai, Yasuko

    AU - Takaoka, Katsuyoshi

    AU - Dong, Fenglan

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