Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3' untranslated region (3'-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3'-UTR reporter transgene to Ca, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node.
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http://dx.doi.org/10.1038/s41467-021-24295-2 | DOI Listing |
Biophys Physicobiol
September 2024
Department of Cell Biology, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Visceral organs in vertebrates are arranged with left-right asymmetry; for example, the heart is located on the left side of the body. Cilia at the node of mouse early embryos play an essential role in determining this left-right asymmetry. Using information from the anteroposterior axis, motile cilia at the central region of the node generate leftward nodal flow.
View Article and Find Full Text PDFPLoS Biol
September 2023
Ecole Polytechnique Fédérale de Lausanne (EPFL) SV ISREC, Lausanne, Switzerland.
Science
January 2023
Laboratory for Organismal Patterning, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
Immotile cilia at the ventral node of mouse embryos are required for sensing leftward fluid flow that breaks left-right symmetry of the body. However, the flow-sensing mechanism has long remained elusive. In this work, we show that immotile cilia at the node undergo asymmetric deformation along the dorsoventral axis in response to the flow.
View Article and Find Full Text PDFNat Commun
September 2021
University of Hohenheim, Institute of Biology, Department of Zoology, Stuttgart, Germany.
Rotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. Ciliary activity of the calcium channel Pkd2 is crucial for flow sensing. How this flow signal is further processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown.
View Article and Find Full Text PDFNat Commun
July 2021
Laboratory for Organismal Patterning, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
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