Regeneration of the Vertebrate Tail

Patrizia Ferretti, UCL Institute of Child Health, London, UK

Published online: January 2011

DOI: 10.1002/9780470015902.a0001101.pub2

Some vertebrates can regenerate their tail, a complex process which involves recruitment and proliferation of progenitor cells from the stump and their subsequent differentiation into the various tissues of the tail. Regeneration is observed only in tails that contain the spinal cord and their ability to regenerate varies among species and with age. Adult tailed amphibians (urodeles) have the most striking regenerative capability and frogs (anurans) can regenerate at larval stages. The spinal cord provides neural progenitor cells from which a new spinal cord will form and in urodeles has a key role in differentiation and morphogenesis of other tail tissues. In anuran tadpoles tail regeneration requires also the presence of the notochord to proceed. Tail regeneration occurs also in lizards, though less faithfully than in urodeles. Recent establishment of effective tracking techniques in amphibians and cloning of their genome is starting to fill the gap in our knowledge of the mechanistic control of tail regeneration.

Key Concepts:

  • The presence of the nervous system is crucial to tail regeneration.
  • Caudal autotomy is associated with regenerative ability in lizards but not in urodeles.
  • Paedomorphosis does not appear to be causally associated with regenerative ability, but continuous growth throughout adulthood correlates with high regenerative capability of all tissue tails including the spinal cord.
  • Neural progenitor cells for regeneration in amphibians maintain an intermediate phenotype between radial glia and ependyma and are likely to be multipotent.
  • Cells in regenerating tails largely maintain their identity and position of origin.
  • Redeployment of certain developmental mechanisms underlies patterning in the regenerating tail.

Keywords: tail; spinal cord; amphibian; lizard; urodeles; anurans

Figure 1. Summary of tail regeneration capability through vertebrate phylogenesis. *Limited knowledge is available concerning tail regeneration in adult lamprey.
Figure 2. Normal and regenerating tail. (a) Schematic longitudinal view of the stump and blastema of the regenerating adult urodele tail. The numbers and arrows indicate the level of the histological cross-sections stained with haematoxylin and eosin shown in (b): 1, normal tail; 2, section through the tail blastema where cartilage condensation (c) is in progress; 3, section close to the tip of the blastema where only the ependymal tube and undifferentiated mesenchymal cells are present.
Figure 3. Schematic representation of an ependymal cell in the spinal cord of adult urodeles.
Figure 4. Cartoon summarising the profile of intermediate filaments expression in radial glia of human and urodele developing spinal cords and ependymoglia of normal adult tails in relation to their expression in the regenerating ependymal tube following tail amputation. The phenotypic conversion to the radial glia phenotype during spinal cord regeneration is indicated by the arrow. It should be noted that the profile of intermediate filaments described in urodeles radial glia parallels that of early radial glia in the developing human spinal cord.
close
 References
    Adams DS, Masi A and Levin M (2007) H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. Development 134: 1323–1335.
    Alibardi L (1995) Muscle differentiation and morphogenesis in the regenerating tail of lizards. Journal of Anatomy 186: 143–151.
    Alibardi L and Lovicu F J (2010) Immunolocalization of FGF1 and FGF2 in the regenerating tail of the lizard Lampropholis guichenoti: implications for FGFs as trophic factors in lizard tail regeneration. Acta Histochemica 12: 459–473.
    Anderson MJ and Waxman SG (1981) Morphology of regenerated spinal cord in Sternarchus albifrons. Cell and Tissue Research 219: 1–8.
    Benraiss A, Arsanto J P, Coulon J and Thouveny Y (1997) Neural crest-like cells originate from the spinal cord during tail regeneration in adult amphibian urodeles. Developmental Dynamics 209: 15–28.
    Bernardini S, Cannata SM and Filoni S (1992) Spinal cord and ganglia regeneration in larval Xenopus laevis following unilateral ablation. Journal für Hirnforschung 33: 241–248.
    Bryant SV and Bellairs AdA (1970a) Development of regenerative ability in the lizard, Lacerta vivipara. American Zoologist 10: 167–173.
    Bryant SV and Bellairs AdA (1970b) Development of regenerative ability in the lizard, Lacerta vivipara. American Zoologist 10: 167–173.
    Chen Y, Lin G and Slack JM (2006) Control of muscle regeneration in the Xenopus tadpole tail by Pax7. Development 133: 2303–2313.
    Chernoff EAG (1996) Spinal cord regeneration: a phenomenon unique to urodeles. International Journal of Developmental Biology 40: 823–831.
    book Clarke JDW and Ferretti P (1998) "CNS regeneration in lower vertebrates". In: Ferretti P and Géraudie J (eds) Cellular and Molecular Basis of Regeneration: From Invertebrates to Humans, pp. 255–269. Chichester, England: Wiley.
    Dinsmore CE (1977) Tail regeneration in the plethodontid salamander, Plethodon cinereus: induced autotomy versus surgical amputation. Journal of Experimental Zoology 199: 163–175.
    Dinsmore CE (1979) Morphogenetic control during tail regeneration in Plethodon cinereus: the role of skeletal muscle. Developmental Biology 72: 244–253.
    Echeverri K, Clarke JD and Tanaka EM (2001) In vivo imaging indicates muscle fiber dedifferentiation is a major contributor to the regenerating tail blastema. Developmental Biology 236: 151–164.
    Echeverri K and Tanaka EM (2002) Ectoderm to mesoderm lineage switching during axolotl tail regeneration. Science 298: 1993–1996.
    Egar M, Simpson SB and Singer M (1970) The growth and differentiation of the regenerating spinal cord of the lizard, Anolis carolinensis. Journal of Morphology 131: 131–151.
    Egar M and Singer M (1972) The role of ependyma in spinal cord regrowth. Experimental Neurology 37: 422–430.
    Fukazawa T, Naora Y, Kunieda T and Kubo T (2009) Suppression of the immune response potentiates tadpole tail regeneration during the refractory period. Development 136: 2323–2327.
    Gargioli C and Slack JM (2004) Cell lineage tracing during Xenopus tail regeneration. Development 131: 2669–2679.
    Geraudie J, Nordlander R, Singer M and Singer J (1988) Early stages of spinal ganglion formation during tail regeneration in the newt, Notophthalmus viridescens. American Journal of Anatomy 183: 359–370.
    Gilbert S, Ruel A, Loranger A and Marceau N (2008) Switch in Fas-activated death signaling pathway as result of keratin 8/18-intermediate filament loss. Apoptosis 13: 1479–1493.
    book Goss JM (1969) "Heads and tails". In: Principles of Regeneration, pp. 191–221. New York: Academic Press.
    Holder N, Clarke JD, Kamalati T and Lane EB (1990) Heterogeneity in spinal radial glia demonstrated by intermediate filament expression and HRP labelling. Journal of Neurocytology 19: 915–928.
    Holtzer S (1956) The inductive ability of the spinal cord in urodele tail regeneration. Journal of Morphology 99: 1–39.
    Iten LE and Bryant SV (1976) Stages of tail regeneration in the adult newt, Notophthalmus viridescens. Journal of Experimental Zoology 196: 283–292.
    Johansson CB, Momma S, Clarke DL et al. (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96: 25–34.
    Jones JE and Corwin JT (1993) Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity. Journal of Neuroscience 13: 1022–1034.
    Kim S and Coulombe PA (2007) Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. Genes & Development 21: 1581–1597.
    Klinger M, Diekmann H, Heinz D et al. (2004) Identification of two NOGO/RTN4 genes and analysis of Nogo-A expression in Xenopus laevis. Molecular and Cellular Neurosciences 25: 205–216.
    Kragl M, Knapp D, Nacu E et al. (2009) Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460: 60–65.
    Lin G, Chen Y and Slack JM (2007) Regeneration of neural crest derivatives in the Xenopus tadpole tail. BMC Developmental Biology 7: 56.
    Lin G and Slack JM (2008) Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. Developmental Biology 316: 323–335.
    Marceau N, Schutte B, Gilbert S et al. (2007) Dual roles of intermediate filaments in apoptosis. Experimental Cell Research 313: 2265–2281.
    McHedlishvili L, Epperlein HH, Telzerow A and Tanaka EM (2007) A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors. Development 134: 2083–2093.
    Nicolas S, Massacrier A, Caubit X, Cau P and Le Parco Y (1996) A Distal-less-like gene is induced in the regenerating central nervous system of the urodeles Pleurodeles waltl. Mechanisms of Development 56: 209–220.
    Nordlander RH and Singer M (1978) The role of ependyma in regeneration of the spinal cord in the urodele amphibian tail. Journal of Comparative Neurology 180: 349–374.
    O'Hara CM, Egar MW and Chernoff EA (1992) Reorganization of the ependyma during axolotl spinal cord regeneration: changes in intermediate filament and fibronectin expression. Developmental Dynamics 193: 103–115.
    O'Neill P, Whalley K and Ferretti P (2004) Nogo and Nogo-66 receptor in human and chick: implications for development and regeneration. Developmental Dynamics 231: 109–121.
    Putta S, Smith JJ, Walker JA et al. (2004) From biomedicine to natural history research: EST resources for ambystomatid salamanders. BMC Genomics 5: 54.
    Quinlan R (2001) Cytoskeletal catastrophe causes brain degeneration. Nature Genetics 27: 10–11.
    Reid B, Song B and Zhao M (2009) Electric currents in Xenopus tadpole tail regeneration. Developmental Biology 335: 198–207.
    Schnapp E, Kragl M, Rubin L and Tanaka EM (2005) Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation and cartilage induction during axolotl tail regeneration. Development 132: 3243–3253.
    Schweigreiter R (2008) The natural history of the myelin-derived nerve growth inhibitor Nogo-A. Neuron Glia Biology 4: 83–89.
    Sehm T, Sachse C, Frenzel C and Echeverri K (2009) miR-196 is an essential early stage regulator of tail regeneration, upstream of key spinal cord patterning events. Developmental Biology 334: 468–480.
    Shao J, Qian X, Zhang C and Xu Z (2009) Fin regeneration from tail segment with musculature, endoskeleton, and scales. Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution 312: 762–769.
    Sharma P and Suresh S (2008) Influence of COX-2-induced PGE2 on the initiation and progression of tail regeneration in Northern House Gecko, Hemidactylus flaviviridis. Folia Biologica (Praha) 54: 193–201.
    Simpson SB Jr (1964) Analysis of tail regeneration in the lizard lygosoma laterale. I. Initiation of regeneration and cartilage differentiation: the role of ependyma. Journal of Morphology 114: 425–435.
    Simpson SB Jr (1970) Studies on regeneration of the lizard's tail. American Zoologist 10: 157–165.
    Smith JJ, Kump DK, Walker JA, Parichy DM and Voss SR (2005) A comprehensive expressed sequence tag linkage map for tiger salamander and Mexican axolotl: enabling gene mapping and comparative genomics in Ambystoma. Genetics 171: 1161–1171.
    Sobkow L, Epperlein HH, Herklotz S, Straube WL and Tanaka EM (2006) A germline GFP transgenic axolotl and its use to track cell fate: dual origin of the fin mesenchyme during development and the fate of blood cells during regeneration. Developmental Biology 290: 386–397.
    Sugiura T, Tazaki A, Ueno N, Watanabe K and Mochii M (2009) Xenopus Wnt-5a induces an ectopic larval tail at injured site, suggesting a crucial role for noncanonical Wnt signal in tail regeneration. Mechanisms of Development 126: 56–67.
    Tanaka EM and Ferretti P (2009) Considering the evolution of regeneration in the central nervous system. Nature Neuroscience. Reviews 10: 713–723.
    Taniguchi Y, Sugiura T, Tazaki A, Watanabe K and Mochii M (2008) Spinal cord is required for proper regeneration of the tail in Xenopus tadpoles. Development, Growth & Differentiation 50: 109–120.
    Wakamatsu Y, Nakamura N, Lee JA, Cole GJ and Osumi N (2007) Transitin, a nestin-like intermediate filament protein, mediates cortical localization and the lateral transport of Numb in mitotic avian neuroepithelial cells. Development 134: 2425–2433.
    Walder S, Zhang F and Ferretti P (2003) Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord. Development Genes and Evolution 213: 625–630.
    Zamora AJ (1978) The ependymal and glial configuration in the spinal cord of urodeles. Anatomy and Embryology (Berlin) 154: 67–82.
    Zhang F, Clarke JD and Ferretti P (2000) FGF-2 up-regulation and proliferation of neural progenitors in the regenerating amphibian spinal cord in vivo. Developmental Biology 225: 381–391.
    Zhang F, Clarke JDW, Santos-Ruiz L and Ferretti P (2002) Differential regulation of FGFRs in the regenerating amphibian spinal cord in vivo. Neuroscience 114: 837–848.
    Zhang F, Ferretti P and Clarke JD (2003) Recruitment of old neurons into the regenerating spinal cord of urodeles. Developmental Dynamics 226: 341–348.
 Further Reading
    book Ferretti P and Géraudie J (ed.) (1998) Cellular and Molecular Basis of Regeneration: From Invertebrates to Humans. Chichester, England: Wiley.
    Basanta D, Miodownik M and Baum B (2008) The evolution of robust development and homeostasis in artificial organisms. PLoS Computational Biology 4: e1000030.
    book Carlson B (2007) Principles of Regenerative Biology. Amsterdam; London: Elsevier.
    Clause AR and Capaldi EA (2006) Caudal autotomy and regeneration in lizards. Journal of Experimental Zoology. Part A, Comparative Experimental Biology 305: 965–973.
    Dinsmore CE (1996) Urodele limb and tail regeneration in early biological thought: an essay on scientific controversy and social change. International Journal of Developmental Biology 40: 621–627.
    Meletis K, Barnabe-Heider F, Carlen M et al. (2008) Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biology 6: e182.
    Mescher AL and Neff AW (2006) Limb regeneration in amphibians: immunological considerations. ScientificWorldJournal 6(suppl. 1): 1–11.
    Pinto L and Gotz M (2007) Radial glial cell heterogeneity – the source of diverse progeny in the CNS. Progress in Neurobiology 83: 2–23.
    Slack JMW (2007) The spark of life: electricity and regeneration. Science's STKE 2007(405): pe54.
    book Stocum D (2006) Regenerative Biology and Medicine Canada. Academic Press: Elsevier.

Related Sub-Topics:

Cell Biology of Organogenesis | Cell Differentiation and Stem Cells | Regeneration: Vertebrates
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Regeneration of the Vertebrate Tail
 
How to Cite close
Ferretti, Patrizia(Jan 2011) Regeneration of the Vertebrate Tail. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001101.pub2]