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WIREs Dev Biol
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Limb regeneration

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Abstract Limb regeneration is observed in certain members of the animal phyla. Some animals keep this ability during their entire life while others lose it at some time during development. How do animals regenerate limbs? Is it possible to find unifying, conserved mechanisms of limb regeneration or have different species evolved distinct means of replacing a lost limb? How is limb regeneration similar or different to limb development? Studies on many organisms, including echinoderms, arthropods, and chordates have provided significant knowledge about limb regeneration. In this focus article, we concentrate on tetrapod limb regeneration as studied in three model amphibians: newts, axolotls, and frogs. We review recent progress on tissue interactions during limb regeneration, and place those findings into an evolutionary context. WIREs Dev Biol 2013, 2:291–300. doi: 10.1002/wdev.73 This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration

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Limb regeneration in salamanders. (a) Time course of forelimb regeneration over 10 weeks in the newt, Notophthalmus viridescens. (Reprinted with permission from Ref 8. Copyright 1969 Academic Press) (b) Brightfield, wholemount image of the regenerating axolotl limb at mid‐bud blastema stage. Dashed line, amputation plane (Knapp and Tanaka, unpublished). (c) Hematoxylin/eosin stained longitudinal section of the regenerating limb blastema (b) (Meersburg, Knapp, and Tanaka, unpublished). Blastema cells appear homogeneous and are encased in epidermis. Dashed line, amputation plane.

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Stage dependence of hindlimb regeneration in the frog, Xenopus laevis. (Reprinted with permission from Ref 3. Copyright 1962 John Wiley & Sons, Inc.)

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Diverging conclusions on muscle‐derived cell fate during axolotl and newt limb regeneration. (a) Cell tracking of fluorescently tagged muscle tissue results in muscle‐specific labeling in the regenerated axolotl limb. Top row, muscle tissue was labeled by transplanting presomitic mesoderm from GFP‐transgenic neurla stage embryos to normal hosts. Middle row, time course of limb regeneration in labeled animals. Bottom row, histological section of regenerated limb shows GFP is restricted to muscle tissue and not found in cartilage or epidermis. (Reprinted with permission from Ref 28. Copyright 2009 Macmillan Publishiing) (b) Cell tracking of virally infected, clonal muscle stem cell cultures during newt limb regeneration. Clonal cell cultures of muscle satellite cells were derived from Notophthalmus viridescens. Cells were infected with adenovirus, and implanted into the regenerating limb blastema. After regeneration, labeled cells were observed in cartilage. First panel: green, Pax7 (arrowheads); red, collagen IV (arrow). Fourth panel: green, GFP; red, collagen II. (Reprinted with permission from Ref 42. Copyright 2010 FASEB)

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