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

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45 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 Dec 1

ASJC Scopus subject areas

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

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    Nakamura, T., Saito, D., Kawasumi, A., Shinohara, K., Asai, Y., Takaoka, K., Dong, F., Takamatsu, A., Belo, J. A., Mochizuki, A., & 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