Limb regeneration in higher vertebrates: Developing a roadmap

Authors

  • Manjong Han,

    1. Dr. Han is a postdoctoral researcher in the Developmental Biology Division of the Department of Cell and Molecular Biology at Tulane University. He received his PhD in developmental biology from Sogang University in Seoul, South Korea
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  • Xiaodong Yang,

    1. Mr. Yang is a PhD student in the Developmental Biology Division of the Department of Cell and Molecular Biology at Tulane University
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  • Gail Taylor,

    1. Dr. Taylor is the assistant program director of the MBRS-RISE research training program in the Biology Department at the University of Texas at San Antonio. She received her PhD in neuroscience from Tulane University
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  • Carol A. Burdsal,

    1. Dr. Burdsal is associate professor in the Developmental Biology Division of the Department of Cell and Molecular Biology at Tulane University. She received her PhD in developmental biology from Duke University
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  • Rosalie A. Anderson,

    1. Dr. Anderson is assistant professor in the Department of Biological Sciences at Loyola University, New Orleans. She received her PhD in cell and molecular biology from Tulane University
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  • Ken Muneoka

    Corresponding author
    1. Dr. Muneoka is professor in the Developmental Biology Division of the Department of Cell and Molecular Biology at Tulane University. He received his PhD in developmental and cell biology from the University of California at Irvine
    • Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118
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    • Fax 504-865-6785


Abstract

We review what is known about amphibian limb regeneration from the prospective of developing strategies for the induction of regeneration in adult mammals. Prominent in urodele amphibian limb regeneration is the formation of a blastema of undifferentiated cells that goes on to reform the limb. The blastema shares many properties with the developing limb bud; thus, the outgrowth phase of regeneration can be thought of as cells going through development again, i.e., redevelopment. Getting to a redevelopment phase in mammals would be a major breakthrough given our extensive understanding of limb development. The formation of the blastema itself represents a transition phase in which limb cells respond to injury by dedifferentiating to become embryonic limb progenitor cells that can undergo redevelopment. During this phase, rapid wound closure is followed by the dedifferentiation of limb cells to form the blastema. Thus, the regeneration process can be divided into a wound-healing/dedifferentiation phase and a redevelopment phase, and we propose that the interface between the wound-healing response and gaining access to developmentally regulated programs (dedifferentiation) lies at the heart of the regeneration problem in mammals. In urodele amphibians, dedifferentiation can occur in all of the tissues of the limb; however, numerous studies lead us to focus on the epidermis, the dermis, and muscle as key regulators of regeneration. Among higher vertebrates, the digit tip in mammals, including humans, is regeneration-competent and offers a unique mammalian model for regeneration. Recent genetic studies in mice identify the Msx1 gene as playing a critical role in the injury response leading to digit tip regeneration. The results from regeneration studies ranging from amphibians to mammals can be integrated to develop a roadmap for mammalian regeneration that has as its focus understanding the phenomenon of dedifferentiation. Anat Rec (Part B: New Anat) 287B:14–24, 2005. © 2005 Wiley-Liss, Inc.

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