title: Wnt/beta-catenin signaling has an essential role in the initiation of limb regeneration.
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/beta-catenin signaling is required for limb regeneration, we created transgenic X. laevis tadpoles that express Dickkopf-1 (Dkk1), a specific inhibitor of Wnt/beta-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/beta-catenin signaling has an essential role during the early stages of limb regeneration, but is not absolutely required after blastema formation.
authors: Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Box 357370, Seattle, WA 98195, USA.
authors: Hitoshi
authors: H
authors: Yokoyama
authors: Hajime
authors: H
authors: Ogino
authors: Cristi L
authors: CL
authors: Stoick-Cooper
authors: Rob M
authors: RM
authors: Grainger
authors: Randall T
authors: RT
authors: Moon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005121:Extremities / Q000502:physiology*; D051526:Fibroblast Growth Factor 10 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D018878:Limb Buds; D011401:Promoter Regions, Genetic; D012038:Regeneration; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
chemical_list: D051526:Fibroblast Growth Factor 10; D018840:HSP70 Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; C555506:WNT3A protein, Xenopus; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D029867:Xenopus Proteins; D051176:beta Catenin; C110182:dkk1 protein, Xenopus; D051524:Fibroblast Growth Factor 8