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Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA
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Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA
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Journal Article
Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA
2012
Overview
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.
During embryonic development, midline fluid flow results in asymmetric nodal gene expression. Using genetic manipulations and mathematical modelling, Nakamura
et al
. find that expression of the nodal antagonist Cerl2 is regulated post-transcriptionally, and that asymmetry is maintained by Wnt-Cerl2 feedback loops.
Publisher
Nature Publishing Group UK,Nature Publishing Group
