Wnt/β-catenin signaling has an essential role in the initiation of limb regeneration

Hitoshi Yokoyama, Hajime Ogino, Cristi L. Stoick-Cooper, Rob M. Grainger, Randall T. Moon

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

Abstract

Anuran (frog) tadpoles and urodeles (newts and salamanders) are the only vertebrates capable of fully regenerating amputated limbs. During the early stages of regeneration these amphibians form a "blastema", a group of mesenchymal progenitor cells that specifically directs the regrowth of the limb. We report that wnt-3a is expressed in the apical epithelium of regenerating Xenopus laevis limb buds, at the appropriate time and place to play a role during blastema formation. To test whether Wnt/β-catenin signaling is required for limb regeneration, we created transgenic X. laevis tadpoles that express Dickkopf-1 (Dkk1), a specific inhibitor of Wnt/β-catenin signaling, under the control of a heat-shock promoter. Heat-shock immediately before limb amputation or during early blastema formation blocked limb regeneration but did not affect the development of contralateral, un-amputated limb buds. When the transgenic tadpoles were heat-shocked following the formation of a blastema, however, they retained the ability to regenerate partial hindlimb structures. Furthermore, heat-shock induced Dkk1 blocked fgf-8 but not fgf-10 expression in the blastema. We conclude that Wnt/β-catenin signaling has an essential role during the early stages of limb regeneration, but is not absolutely required after blastema formation.

Original languageEnglish
Pages (from-to)170-178
Number of pages9
JournalDevelopmental Biology
Volume306
Issue number1
DOIs
Publication statusPublished - 2007 Jun 1
Externally publishedYes

Keywords

  • Limb
  • Regeneration
  • Transgenic
  • Wnt/β-catenin signaling
  • Xenopus laevis
  • fgf-10
  • fgf-8

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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