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 () and Hiroshi Hamada
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Tetsuya Nakamura: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)
Daisuke Saito: Theoretical Biology Laboratory, RIKEN Advanced Science Institute
Aiko Kawasumi: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)
Kyosuke Shinohara: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)
Yasuko Asai: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)
Katsuyoshi Takaoka: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)
Fenglan Dong: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)
Atsuko Takamatsu: Waseda University
Jose Antonio Belo: IBB–Institute for Biotechnology and Bioengineering, Centro de Biomedicina Moleculare Estrutural, Universidade do Algarve
Atsushi Mochizuki: Theoretical Biology Laboratory, RIKEN Advanced Science Institute
Hiroshi Hamada: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST)

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms2319

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