Wnt signaling regulates left–right axis formation in the node of mouse embryos

The node triggers formation of the left–right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be reg...

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Bibliographic Details
Published in:Developmental biology 2013-08, Vol.380 (2), p.222-232
Main Authors: Kitajima, Keiko, Oki, Shinya, Ohkawa, Yasuyuki, Sumi, Tomoyuki, Meno, Chikara
Format: Article
Language:English
Subjects:
Animals
binding sites
Body Patterning
Female
gene expression
Hepatocyte Nuclear Factor 3-beta - physiology
Immunoglobulin J Recombination Signal Sequence-Binding Protein - physiology
Intercellular Signaling Peptides and Proteins - physiology
Left–right axis
Mice
Mice, Inbred ICR
Mouse embryo
Node
Notch signaling
Wnt
Wnt Signaling Pathway - physiology
Wnt3 Protein - physiology
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Summary:The node triggers formation of the left–right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell-specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left–right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt-β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left–right difference in Nodal activity at the node for further amplification in lateral plate mesoderm. •Wnt3 is left–right asymmetrically expressed in crown cells of the node.•Wnt3 expression in the node is regulated by the combined actions of Rbpj and Foxa2.•DAPT treatment extinguishes the expression of L–R axis–related genes in crown cells.•Canonical Wnt signaling suppresses the expression of Cerl2.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2013.05.011