TY - JOUR
T1 - Wnt/β-catenin signaling has an essential role in the initiation of limb regeneration
AU - Yokoyama, Hitoshi
AU - Ogino, Hajime
AU - Stoick-Cooper, Cristi L.
AU - Grainger, Rob M.
AU - Moon, Randall T.
N1 - Funding Information:
We thank Dr. Stefan Hoppler for providing the Xenopus hsp70 promoter and for advice on how to control this promoter, and Dr. Gilbert Weidinger for the zebrafish Dkk1 clone and for discussions. We thank Travis Biechele for technical help with luciferase assays, Jeanot Muster and Jerry Ament for excellent frog care, and Dr. Charlotte Hubbert for reading the manuscript. We thank Drs. Hiroyuki Ide and Koji Tamura for the gift of Xenopus fgf-10 , fgf-8 , Lmx-1 , Hoxa-13 and msx-2 clones. HY was supported by JSPS Research Fellowships for Young Scientists and JSPS Postdoctoral Fellowships for Research Abroad. C. S. C. is a recipient of a NIH-funded Cardiovascular Pathology Training Grant. This work was supported by National Institutes of Health award RO1 GM073887-01. RTM is an investigator of the HHMI.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
KW - Limb
KW - Regeneration
KW - Transgenic
KW - Wnt/β-catenin signaling
KW - Xenopus laevis
KW - fgf-10
KW - fgf-8
UR - http://www.scopus.com/inward/record.url?scp=34249292278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249292278&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2007.03.014
DO - 10.1016/j.ydbio.2007.03.014
M3 - Article
C2 - 17442299
AN - SCOPUS:34249292278
VL - 306
SP - 170
EP - 178
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -