Van Gogh-like (Vangl) and Prickle (Pk) are core components of the non-canonical Wnt planar cell polarity pathway that controls epithelial polarity and cell migration. Studies in vertebrate model systems have suggested that Vangl and Pk may also inhibit signaling through the canonical Wnt/β-catenin pathway, but the functional significance of this potential cross-talk is unclear. In the nematode C. elegans, the Q neuroblasts and their descendants migrate in opposite directions along the anteroposterior body axis. The direction of these migrations is specified by Wnt signaling, with activation of canonical Wnt signaling driving posterior migration, and non-canonical Wnt signaling anterior migration. Here, we show that the Vangl ortholog VANG-1 influences the Wnt signaling response of the Q neuroblasts by negatively regulating canonical Wnt signaling. This inhibitory activity depends on a carboxy-terminal PDZ binding motif in VANG-1 and the Dishevelled ortholog MIG-5, but is independent of the Pk ortholog PRKL-1. Moreover, using Vangl1 and Vangl2 double mutant cells, we show that a similar mechanism acts in mammalian cells. We conclude that cross-talk between VANG-1/Vangl and the canonical Wnt pathway is an evolutionarily conserved mechanism that ensures robust specification of Wnt signaling responses.

• MeSH
• beta-katenin genetika   metabolismus   MeSH
• buněčný rodokmen MeSH
• Caenorhabditis elegans cytologie   genetika   metabolismus   MeSH
• fosfoproteiny genetika   metabolismus   MeSH
• geneticky modifikovaná zvířata MeSH
• geny helmintů MeSH
• homeodoménové proteiny genetika   metabolismus   MeSH
• intracelulární signální peptidy a proteiny genetika   metabolismus   MeSH
• mutace MeSH
• nervové kmenové buňky cytologie   metabolismus   MeSH
• polarita buněk genetika   fyziologie   MeSH
• protein dishevelled genetika   metabolismus   MeSH
• proteiny Caenorhabditis elegans genetika   metabolismus   MeSH
• rozvržení tělního plánu genetika   fyziologie   MeSH
• signální dráha Wnt genetika   fyziologie   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH