Under the leadership of HAMADA Hiroshi , Professor, Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, MOCHIZUKI Atsushi , Chief Fellow, Riken, SAITO Daisuke , Researcher, Waseda University, TAKAMATSU Atsuko , Professor, and Algarve University, Portugal, a group of researchers have clarified in mice experiments that a minuscule fluid flow controlling the stability of gene products caused asymmetric gene expression in the processes involved in the breaking of left-right (L-R) symmetry. It is known that fluid flow in embryogenesis controls gene expressions; however, the precise action of fluid flow to gene expression has been unknown. This research has clarified part of its mechanism and it is a big step toward the possible clarification of the process of determining the left–right arrangement of body parts.
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.

Related link :

• Development Genetics Group