Wnt3a links left-right determination with segmentation and anteroposterior axis elongation.
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.
Nakaya
Masa-aki
MA
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH Frederick, MD 21702, USA.
Biris
Kristin
K
Tsukiyama
Tadasuke
T
Jaime
Shaulan
S
Rawls
J Alan
JA
Yamaguchi
Terry P
TP
D000818:Animals; D019521:Body Patterning; D002923:Cilia / Q000502:physiology; D004622:Embryo, Mammalian / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009154:Mutation; D055457:Nodal Protein; D051880:Receptors, Notch / Q000378:metabolism; D019170:Somites / Q000502:physiology*; D050396:TRPP Cation Channels / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism
D055457:Nodal Protein; D051880:Receptors, Notch; D050396:TRPP Cation Channels; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; C526008:Nodal protein, mouse; C555511:Wnt3a protein, mouse