Ectodermal Wnt3/β-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge (original) (raw)

  1. Jeffery R. Barrow1,
  2. Kirk R. Thomas2,
  3. Oreda Boussadia-Zahui3,4,
  4. Robert Moore3,5,
  5. Rolf Kemler3,
  6. Mario R. Capecchi2, and
  7. Andrew P. McMahon1,6
  8. 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA; 2Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA;3Department of Molecular Embryology, Max-Planck Institute of Immunobiology, D-79108 Freiberg, Germany.

Abstract

The formation of the apical ectodermal ridge (AER) is critical for the distal outgrowth and patterning of the vertebrate limb. Recent work in the chick has demonstrated that interplay between the Wnt_and Fgf signaling pathways is essential in the limb mesenchyme and ectoderm in the establishment and perhaps the maintenance of the AER. In the mouse, whereas a role for Fgfs for AER establishment and function has been clearly demonstrated, the role of_Wnt/β-catenin signaling, although known to be important, is obscure. In this study, we demonstrate that Wnt3, which is expressed ubiquitously throughout the limb ectoderm, is essential for normal limb development and plays a critical role in the establishment of the AER. We also show that the conditional removal of_β-catenin_ in the ventral ectodermal cells is sufficient to elicit the mutant limb phenotype. In addition, removing_β-catenin_ after the induction of the ridge results in the disappearance of the AER, demonstrating the requirement for continued_β-catenin_ signaling for the maintenance of this structure. Finally, we demonstrate that Wnt/β-catenin signaling lies upstream of the Bmp signaling pathway in establishment of the AER and regulation of the dorsoventral polarity of the limb.

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