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

被引:98
作者
Yokoyama, Hitoshi
Ogino, Hajime
Stoick-Cooper, Cristi L.
Grainger, Rob M.
Moon, Randall T.
机构
[1] Univ Washington, Sch Med, Howard Hughes Med Inst, Dept Pharmacol,Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA
[2] Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA
关键词
Xenopus laevis; limb; regeneration; Wnt/beta-catenin signaling; transgenic; fgf-8; fgf-10;
D O I
10.1016/j.ydbio.2007.03.014
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Heatshock 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. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:170 / 178
页数:9
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