Interaction between Wnt and TGF-beta signalling pathways during formation of Spemann's organizer

Nature. 2000 Feb 17;403(6771):781-5. doi: 10.1038/35001602.


Members of the Wnt and TGF-beta superfamilies regulate both cell fate and proliferation during development and tissue maintenance. In the early amphibian embryo, the Wnt and TGF-beta superfamily signalling cascades are required for the establishment of a dorsal signalling centre, Spemann's organizer. Intracellular proteins of both pathways, upon activation, translocate to the nucleus to participate in transcription. Here we show that beta-catenin and Lef1/Tcf, which are downstream components of the Wnt signalling cascade, form a complex with Smad4, an essential mediator of signals initiated by members of the TGF-beta growth factor superfamily. In Xenopus, this interaction directly and synergistically affects expression of the twin (Xtwn) gene during formation of the organizer. This is, to our knowledge, the first demonstration of a physical interaction between TGF-beta and Wnt signalling components in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • DNA Footprinting
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Nerve Growth Factors
  • Organizers, Embryonic*
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction*
  • Smad Proteins
  • Smad4 Protein
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Wnt Proteins
  • Xenopus
  • Xenopus Proteins*
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nerve Growth Factors
  • Proto-Oncogene Proteins
  • SIA1 protein, Xenopus
  • Smad Proteins
  • Smad4 Protein
  • Smad4 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • beta Catenin
  • sia2 protein, Xenopus
  • smad4.1 protein, Xenopus
  • smad4.2 protein, Xenopus
  • smad4a protein, zebrafish