title: Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA.
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.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan. t-nakamura@fbs.osaka-u.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saito
authors.forename: Aiko
authors.initials: A
authors.lastname: Kawasumi
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Shinohara
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Asai
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takaoka
authors.forename: Fenglan
authors.initials: F
authors.lastname: Dong
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takamatsu
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Belo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mochizuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D025461:Feedback, Physiological; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D060508:Wnt3 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C119003:Dte protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D060508:Wnt3 Protein