WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo

Cell. 2001 Mar 23;104(6):891-900. doi: 10.1016/s0092-8674(01)00285-9.


A regulatory loop between the fibroblast growth factors FGF-8 and FGF-10 plays a key role in limb initiation and AER induction in vertebrate embryos. Here, we show that three WNT factors signaling through beta-catenin act as key regulators of the FGF-8/FGF-10 loop. The Wnt-2b gene is expressed in the intermediate mesoderm and the lateral plate mesoderm in the presumptive chick forelimb region. Cells expressing Wnt-2b are able to induce Fgf-10 and generate an extra limb when implanted into the flank. In the presumptive hindlimb region, another Wnt gene, Wnt-8c, controls Fgf-10 expression, and is also capable of inducing ectopic limb formation in the flank. Finally, we also show that the induction of Fgf-8 in the limb ectoderm by FGF-10 is mediated by the induction of Wnt-3a. Thus, three WNT signals mediated by beta-catenin control both limb initiation and AER induction in the vertebrate embryo.

Publication types

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

MeSH terms

  • Animals
  • Avian Proteins
  • Chick Embryo / physiology*
  • Cytoskeletal Proteins / physiology
  • Ectoderm / physiology
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology*
  • Gene Expression Regulation, Developmental
  • Limb Buds / physiology*
  • Mesoderm / physiology
  • Mitogens / physiology
  • Morphogenesis
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Signal Transduction
  • Trans-Activators*
  • Wings, Animal / embryology
  • Wnt Proteins
  • Wnt2 Protein
  • Zebrafish Proteins*
  • beta Catenin


  • Avian Proteins
  • Cytoskeletal Proteins
  • Fibroblast Growth Factor 10
  • Mitogens
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Wnt-2b protein, Gallus gallus
  • Wnt2 Protein
  • Zebrafish Proteins
  • beta Catenin
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors