Article

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

University of Washington Seattle, Seattle, Washington, United States
Developmental Biology (Impact Factor: 3.64). 07/2007; 306(1):170-8. DOI: 10.1016/j.ydbio.2007.03.014
Source: PubMed

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.

Full-text

Available from: Randall T Moon, Jun 11, 2015
0 Followers
 · 
150 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Urodele amphibians are unique adult vertebrates because they are able to regenerate body parts after amputation. Studies of urodele limb regeneration, the key model system for vertebrate regeneration, have led to an understanding of the origin of blastema cells and the importance of positional interactions between blastema cells in the control of growth and pattern formation. Progress is now being made in the identification of the signaling pathways that regulate dedifferentiation, blastema morphogenesis, growth and pattern formation. Members of the Wnt family of secreted proteins are expressed in developing and regenerating limbs, and have the potential to control growth, pattern formation and differentiation. We have studied the expression of two non-canonical Wnt genes, Wnt-5a and Wnt-5b. We report that they are expressed in equivalent patterns during limb development and limb regeneration in the axolotl (Ambystoma mexicanum), and during limb development in other tetrapods, implying conservation of function. Our analysis of the effects of ectopic Wnt-5a expression is consistent with the hypothesis that canonical Wnt signaling functions during the early stages of regeneration to control the dedifferentiation of stump cells giving rise to the regeneration-competent cells of the blastema.
    Development Growth and Regeneration 06/2008; 50(4):289-97. DOI:10.1111/j.1440-169X.2008.01000.x · 2.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Comprehending the diversity of the regenerative potential across metazoan phylogeny represents a fundamental challenge in biology. Invertebrates like Hydra and planarians exhibit amazing feats of regeneration, in which an entire organism can be restored from minute body segments. Vertebrates like teleost fish and amphibians can also regrow large sections of the body. While this regenerative capacity is greatly attenuated in mammals, there are portions of major organs that remain regenerative. Regardless of the extent, there are common basic strategies to regeneration, including activation of adult stem cells and proliferation of differentiated cells. Here, we discuss the cellular features and molecular mechanisms that are involved in regeneration in different model organisms, including Hydra, planarians, zebrafish and newts as well as in several mammalian organs. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.
    Journal of Genetics and Genomics 02/2015; 42(2). DOI:10.1016/j.jgg.2014.12.002 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Visceral regeneration in sea cucumbers has been studied since early last century; however, it is only within the last 15 years that real progress has been made in understanding the cellular and molecular events involved. In the present review, we bring together these recent studies, providing readers with basic information on the anatomy and histology of the normal gut and detailing the changes in tissue organization and gene expression that occur during the regenerative process. We discuss the nature and possible sources of cells involved in the formation of the intestinal regenerate as well as the role of cell death and proliferation in this process. In addition, we compare gut formation during regeneration and during embryogenesis. Finally, we describe the molecular studies that have helped advance regenerative studies in holothurians and integrate the gene expression information with data on cellular events. Studies on visceral regeneration in these echinoderms provide a unique view that complements regeneration studies in other animal phyla, which are mainly focused on whole-animal regeneration or appendage regeneration.
    Biological Bulletin 08/2011; 221(1):93-109. · 1.57 Impact Factor