Wnt3a links left-right determination with segmentation and anteroposterior axis elongation

Development. 2005 Dec;132(24):5425-36. doi: 10.1242/dev.02149. Epub 2005 Nov 16.

Abstract

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/beta-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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Body Patterning*
  • Cilia / physiology
  • Embryo, Mammalian / physiology
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Transgenic
  • Morphogenesis
  • Mutation
  • Nodal Protein
  • Receptors, Notch / metabolism
  • Somites / physiology*
  • TRPP Cation Channels / metabolism
  • Transforming Growth Factor beta / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / physiology*
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / metabolism

Substances

  • Nodal Protein
  • Nodal protein, mouse
  • Receptors, Notch
  • TRPP Cation Channels
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin
  • polycystic kidney disease 1 protein