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First published online 16 November 2005
doi: 10.1242/dev.02149
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1 Cancer and Developmental Biology Laboratory, Center for Cancer Research,
National Cancer Institute-Frederick, NIH Frederick, MD 21702, USA
2 School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501,
USA
* Author for correspondence (e-mail: tyamaguchi{at}ncifcrf.gov)
Accepted 23 September 2005
The alignment of the left-right (LR) body axis relative to the anteroposterior (AP) and dorsoventral (DV) axes is central to the organization of the vertebrate body plan and is controlled by the node/organizer. Somitogenesis plays a key role in embryo morphogenesis as a principal component of AP elongation. How morphogenesis is coupled to axis specification is not well understood. We demonstrate that Wnt3a is required for LR asymmetry. Wnt3a activates the Delta/Notch pathway to regulate perinodal expression of the left determinant Nodal, while simultaneously controlling the segmentation clock and the molecular oscillations of the Wnt/ß-catenin and Notch pathways. We provide evidence that Wnt3a, expressed in the primitive streak and dorsal posterior node, acts as a long-range signaling molecule, directly regulating target gene expression throughout the node and presomitic mesoderm. Wnt3a may also modulate the symmetry-breaking activity of mechanosensory cilia in the node. Thus, Wnt3a links the segmentation clock and AP axis elongation with key left-determining events, suggesting that Wnt3a is an integral component of the trunk organizer.
Key words: Mouse, Wnt3a, Left-right determination
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