Wnt/beta-catenin signaling has an essential role in the initiation of limb regeneration.
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.
Yokoyama
Hitoshi
H
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.
Ogino
Hajime
H
Stoick-Cooper
Cristi L
CL
Grainger
Rob M
RM
Moon
Randall T
RT
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*
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