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Considering the evolution of regeneration in the central nervous system

Nature Reviews Neuroscience volume 10, pages 713–723 (2009)Cite this article

Key Points

  • CNS regeneration is a diverse and varied trait that is observed in multiple vertebrates. The profile of regenerating species could be consistent with the presence of regeneration in the ancestral vertebrate and loss during evolution.

  • Anamniotes (that is, lower vertebrates) such as fish and salamanders can undergo not only axon regrowth, but also new neurogenesis after brain and spinal cord injury. Frogs lose this ability around metamorphosis and birds and mammals during embryonic development. Lizards present an intermediate character, with a capacity for extensive neurogenesis in the brain but defective spinal cord regeneration. An important question is whether the loss of regeneration during development in frogs is evolutionarily related to the loss seen in birds and mammals.

  • Regeneration requires glial cells lining the central lumen to reseal the wound in a way that reconstitutes the stem cell pool for neurogenesis. The profile of glia, their wound-healing ability and the extracellular environment stimulating wound healing has changed over evolution.

  • Regeneration also depends on glia maintaining and re-accessing expression of embryonic morphogens and their transduction pathways to stimulate cell growth, re-patterning and diversification to regenerate the CNS. Access to these embryonic programmes has become limited in mammals.

  • Wound healing and regeneration may not be traits that were actively selected for but rather the by-products of a dynamic developmental system of cell interactions, and, in later life stages, the physiology of continued tissue growth.

  • We speculate that the main selective pressures that have acted on regeneration are how first wounds are healed, and second, whether glial cells can retain access to embryonic genetic programmes to undertake neurogenesis. The latter may have limited CNS complexity in regenerative organisms.

Abstract

For many years the mammalian CNS has been seen as an organ that is unable to regenerate. However, it was also long known that lower vertebrate species are capable of impressive regeneration of CNS structures. How did this situation arise through evolution? Increasing cellular and molecular understanding of regeneration in different animal species coupled with studies of adult neurogenesis in mammals is providing a basis for addressing this question. Here we compare CNS regeneration among vertebrates and speculate on how this ability may have emerged or been restricted.

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Figure 1: Different cellular modes of regenerating spinal cord structures after amputation.
Figure 2: Neural progenitors in spinal cord development and regeneration.
Figure 3: Regeneration in the forebrain after neurotoxin damage versus injury.
Figure 4: Phylogenetic overview of CNS regeneration ability.

References

  1. Lenhoff, H. M. & Lenhoff, S. G. in A History of Regeneration Research: Milestones in the Evolution of a Science (Ed. Dinsmore C. E.) (Cambridge University Press, Cambridge, 1991).

    Google Scholar 

  2. Goss, R. J., The evolution of regeneration: adaptive or inherent? J. Theor. Biol. 159, 241–260 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. Sanchez Alvarado, A., Regeneration in the metazoans: why does it happen. Bioessays 22, 578–590 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Brockes, J. P., Kumar, A. & Velloso, C. P., Regeneration as an evolutionary variable. J. Anat. 199, 3–11 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Brockes, J. P. & Kumar, A., Comparative aspects of animal regeneration. Annu. Rev. Cell Dev. Biol. 24, 525–549 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Lurie, D. I. & Selzer, M. E., Axonal regeneration in the adult lamprey spinal cord. J. Comp. Neurol. 306, 409–416 (1991).

    Article  CAS  PubMed  Google Scholar 

  7. Rehermann, M. I., Marichal, N., Russo, R. E. & Trujillo-Cenóz, O., Neural reconnection in the transected spinal cord of the freshwater turtle Trachemys dorbignyi. J. Comp. Neurol. 515, 197–214 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kirsche, W., in Neural Tissue Transplantation Research (Eds R. B. Wallace & Das. G. D.) 65–104 (Springer, Berlin, 1995).

    Google Scholar 

  9. Molowny, A., Nacher, J. & Lopez- García, C., Reactive neurogenesis during regeneration of the lesioned medial cerebral cortex of lizards. Neuroscience 68, 823–836 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Endo, T., Yoshino, J., Kado, K. & Tochinai, S., Brain regeneration in anuran amphibians. Dev. Growth Differ. 49, 121–129 (2007).

    Article  PubMed  Google Scholar 

  11. Chojnacki, A. K., Mak, G. K. & Weiss, S., Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both? Nature Rev. Neurosci. 10, 153–163 (2009).

    Article  CAS  Google Scholar 

  12. Alvarez-Buylla, A., García-Verdugo, J. M. & Tramontin, A. D., A unified hypothesis on the lineage of neural stem cells. Nature Rev. Neurosci. 2, 287–293 (2001).

    Article  CAS  Google Scholar 

  13. Spallanzani, L., Prodromo di un opera da imprimersi sopra la riproduzioni animali. (Bartolomeo Soliani, Modena, 1768) (in italian).

    Book  Google Scholar 

  14. Roguski, H., Regeneration of the tail of tadpole Xenopus laevis. Folia Biol. (Krakow) 1, 7–22 (1953).

    CAS  Google Scholar 

  15. Niazi, I. A., The histology of tail regeneration in the ammocoetes. Can. J. Zool. 41, 125–151 (1963).

    Article  Google Scholar 

  16. Iten, L. E. & Bryant, S. V., Stages of tail regeneration in the adult newt, Notophthalmus viridescens. J. Exp. Zool. 196, 283–292 (1976).

    Article  CAS  PubMed  Google Scholar 

  17. Anderson, M. J. & Waxman, S. G., Morphology of regenerated spinal cord in Sternarchus albifrons. Cell Tissue Res. 219, 1–8 (1981).

    Article  CAS  PubMed  Google Scholar 

  18. Filoni, S. & Bosco, L., Comparative analysis of the regenerative capacity of caudal spinal cord in larvae of serveral Anuran amphibian species. Acta Embryol. Morphol. Exp. 2, 199–226 (1981).

    CAS  PubMed  Google Scholar 

  19. Geraudie, J., Nordlander, R., Singer, M. & Singer, J., Early stages of spinal ganglion formation during tail regeneration in the newt, Notophthalmus viridescens. Am. J. Anat. 183, 359–370 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Egar, M., Simpson, S. B. & Singer, M., The growth and differentiation of the regenerating spinal cord of the lizard, Anolis carolinensis. J. Morphol. 131, 131–151 (1970).

    Article  CAS  PubMed  Google Scholar 

  21. Zupanc, G. K., Kompass, K. S., Horschke, I., Ott, R. & Schwarz, H., Apoptosis after injuries in the cerebellum of adult teleost fish. Exp. Neurol. 152, 221–230 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Lin, G., Chen, Y. & Slack, J. M., Regeneration of neural crest derivatives in the Xenopus tadpole tail. BMC Dev. Biol. 7, 56 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Russo, R. E., Fernandez, A., Reali, C., Radmilovich, M. & Trujillo- Cenóz, O., Functional and molecular clues reveal precursor-like cells and immature neurones in the turtle spinal cord. J. Physiol. 560 (Pt 3), 831–838 (2004).

  24. Font, E., García-Verdugo, J. M., Alcántara, S. & López- García, C., Neuron regeneration reverses 3-acetylpyridine-induced cell loss in the cerebral cortex of adult lizards. Brain Research 551, 230–235 (1991).

    Article  CAS  PubMed  Google Scholar 

  25. Gallien, L. & Beetschen, J. C., Extent and limits of the regenerative power of the extremities in Xenopus laevis Daudin after metamorphosis. C. R. Seances Soc. Biol. Fil. 145, 874–876 (1951) (in french).

    CAS  PubMed  Google Scholar 

  26. Beattie, M. S., Bresnahan, J. C. & Lopate, G., Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs. J. Neurobiol. 21, 1108–1122 (1990).

    Article  CAS  PubMed  Google Scholar 

  27. Filoni, S. & Gibertini, G., A study of the regenerative capacity of the central nervous system of anuran amphibia in relation to their stage of development. I. Observations on the regeneration of the optic lobe of Xenopus laevis (Daudin) in the larval stages. Arch. Biol. (Liege) 80, 369–411 (1969).

    CAS  Google Scholar 

  28. Mizell, M., Limb regeneration: induction in the newborn opossum. Science 161, 283–286 (1968).

    Article  CAS  PubMed  Google Scholar 

  29. Nicholls, J. & Saunders, N., Regeneration of immature mammalian spinal cord after injury. Trends Neurosci. 19, 229–234 (1996).

    Article  CAS  PubMed  Google Scholar 

  30. Butler, E. G. & Ward, M. B. Reconstitution of the spinal cord after ablation in adult Triturus. Dev. Biol. 15, 464–486 (1967).

    Article  CAS  PubMed  Google Scholar 

  31. Egar, M. & Singer, M., The role of ependyma in spinal cord after ablation in adult Triturus. Exp. Neurol. 37, 422–430 (1972).

    Article  CAS  PubMed  Google Scholar 

  32. O'Hara, C. M., Egar, M. W. & Chernoff, E. A., Reorganization of the ependyma during axolotl spinal cord regeneration: changes in intermediate filament and fibronectin expression. Dev. Dyn. 193, 103–115 (1992).

    Article  CAS  PubMed  Google Scholar 

  33. Walder, S., Zhang, F. & Ferretti, P., Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord. Dev. Genes Evol. 213, 625–630 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Liuzzi, F. J. & Miller, R. H., Radially oriented astrocytes in the normal adult rat spinal cord. Brain Res. 403, 385–388 (1987).

    Article  CAS  PubMed  Google Scholar 

  35. Barrett, C. P., Guth, L., Donati, E. J. & Krikorian, J. G., Astroglial reaction in the gray matter lumbar segments after midthoracic transection of the adult rat spinal cord. Exp. Neurol. 73, 365–377 (1981).

    Article  CAS  PubMed  Google Scholar 

  36. Bernstein, J. J., Getz, R., Jefferson, M. & Kelemen, M., Astrocytes secrete basal lamina after hemisection of rat spinal cord. Brain Res. 327, 135–141 (1985).

    Article  CAS  PubMed  Google Scholar 

  37. Miller, R. H., David, S., Patel, R., Abney, E. R. & Raff, M. C., A quantitative immunohistochemical study of macroglial cell development in the rat optic nerve: in vivo evidence for two distinct astrocyte lineages. Dev. Biol. 111, 35–41 (1985).

    Article  CAS  PubMed  Google Scholar 

  38. Meletis, K. et al., Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol. 6, e182 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Zamora, A. J., The ependymal and glial configuration in the spinal cord of urodeles. Anat. Embryol. (Berl.) 154, 67–82 (1978).

    Article  CAS  Google Scholar 

  40. Sims, T. J., Gilmore, S. A. & Waxman, S. G., Radial glia give rise to perinodal processes. Brain Res. 549, 25–35 (1991).

    Article  CAS  PubMed  Google Scholar 

  41. García-Verdugo, J. M. et al., The proliferative ventricular zone in adult vertebrates: a comparative study using reptiles, birds, and mammals. Brain Res. Bull. 57, 765–775 (2002).

    Article  PubMed  Google Scholar 

  42. Alvarez-Buylla, A., Buskirk, D. R. & Nottebohm, F., Monoclonal antibody reveals radial glia in adult avian brain. J. Comp. Neurol. 264, 159–170 (1987).

    Article  CAS  PubMed  Google Scholar 

  43. Eggenschwiler, J. T. & Anderson, K. V., Cilia and developmental signaling. Annu. Rev. Cell Dev. Biol. 23, 345–373 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mirzadeh, Z., Merkle, F. T., Soriano-Navarro, M., Garcia-Verdugo, J. M. & Alvarez-Buylla, A., Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3, 265–278 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yoshino, J. & Tochinai, S., Successful reconstitution of the non-regenerating adult telencephalon by cell transplantation in Xenopus laevis. Dev. Growth Differ. 46, 523–534 (2004).

    Article  PubMed  Google Scholar 

  46. Whalley, K., O'Neill, P. & Ferretti, P., Changes in response to spinal cord injury with development: vascularization, haemorrhage and apoptosis. Neuroscience 137, 821–832 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Keirstead, H. S., Hasan, S. J., Muir, G. D. & Steeves, J. D., Suppression of the onset of myelination extends the permissive period for the functional repair of embryonic spinal cord. Proc. Natl Acad. Sci. USA 89, 11664–11668 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Whalley, K., Gögel, S., Lange, S. & Ferretti, P., Changes in progenitor populations and ongoing neurogenesis in the regenerating chick spinal cord. Dev. Biol. 332, 234–245 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Holder, N. & Clarke, J. D., Is there a correlation between continuous neurogenesis and directed axon regeneration in the vertebrate nervous system? Trends Neurosci. 11, 94–99 (1988).

    Article  CAS  PubMed  Google Scholar 

  50. Ferretti, P., Zhang, F. & O'Neill, P., Changes in spinal cord regeneration through phylogenesis and development: lessons to be learnt. Dev. Dyn. 226, 245–256 (2003).

    Article  PubMed  Google Scholar 

  51. Buffo, A. et al., Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc. Natl Acad. Sci. USA 105, 3581–3586 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Carlen, M. et al., Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nature Neurosci. 12, 259–267 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Mescher, A. L. & Neff, A. W., Limb regeneration in amphibians: immunological considerations. ScientificWorldJournal 6 (Suppl. 1), 1–11 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Fukazawa, T., Naora, Y., Kunieda, T. & Kubo, T., Suppression of the immune response potentiates tadpole tail regeneration during the refractory period. Development 136, 2323–2327 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Basanta, D., Miodownik, M. & Baum, B., The evolution of robust development and homeostasis in artificial organisms. PLoS Comput. Biol. 4, e1000030 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Holtzer, S., The inductive activiy of the spinal cord in urodele tail regeneration. J. Morphol. 99, 1–39 (1956).

    Article  Google Scholar 

  57. Mchedlishvili, L., Epperlein, H., Telzerow, A. & Tanaka, E., A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors. Development 134, 2083–2093 (2007).

    Article  CAS  PubMed  Google Scholar 

  58. Schnapp, E., Kragl, M., Rubin, L. & Tanaka, E. M., Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation and cartilage induction during axolotl tail regeneration. Development 132, 3243–3253 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Bourikas, D. et al., Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord. Nature Neurosci. 8, 297–304 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Yamamoto, S. et al., Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord. J. Neurosci. 21, 9814–9823 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Arsanto, J. P. et al., Formation of the peripheral nervous system during tail regeneration in urodele amphibians: ultrastructural and immunohistochemical studies of the origin of the cells. J. Exp. Zool. 264, 273–292 (1992).

    Article  CAS  PubMed  Google Scholar 

  62. Koussoulakos, S., Margaritis, L. H. & Anton, H., Origin of renewed spinal ganglia during tail regeneration in urodeles. Dev. Neurosci. 21, 134–139 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Sugiura, T. et al., Differential gene expression between the embryonic tail bud and regenerating larval tail in Xenopus laevis. Dev. Growth Differ. 46, 97–105 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Yakushiji, N. et al., Correlation between Shh expression and DNA methylation status of the limb-specific Shh enhancer region during limb regeneration in amphibians. Dev. Biol. 312, 171–182 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Carlson, B. M., The regeneration of axolotl limbs covered by frog skin. Dev. Biol. 90, 435–440 (1982).

    Article  CAS  PubMed  Google Scholar 

  66. Sessions, S. K., Gardiner, D. M. & Bryant, S. V., Compatible limb patterning mechanisms in urodeles and anurans. Dev. Biol. 131, 294–301 (1989).

    Article  CAS  PubMed  Google Scholar 

  67. Gould, S. J., Ontogeny and phylogeny. (Harvard University Press, Boston, 1977).

    Google Scholar 

  68. Roth, G., Blanke, J. & Wake, D. B., Cell size predicts morphological complexity in the brains of frogs and salamanders. Proc. Natl Acad. Sci. USA 91, 4796–4800 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Roth, G., Nishikawa, K. C. & Wake, D. B., Genome size, secondary simplification, and the evolution of the brain in salamanders. Brain Behav. Evol. 50, 50–59 (1997).

    Article  CAS  PubMed  Google Scholar 

  70. Martin, C. C. & Gordon, R., Differentiation trees, a junk DNA molecular clock, and the evolution of neoteny in salamanders. J. Evol. Biol. 8, 339–354 (1995).

    Article  Google Scholar 

  71. Paris, M. & Laudet, V., The history of a developmental stage: metamorphosis in chordates. Genesis 46, 657–672 (2008).

    Article  CAS  PubMed  Google Scholar 

  72. Lang, D. M. & Stuermer, C. A., Adaptive plasticity of Xenopus glial cells in vitro and after CNS fiber tract lesions in vivo. Glia 18, 92–106 (1996).

    Article  CAS  PubMed  Google Scholar 

  73. Lang, D. M., Rubin, B. P., Schwab, M. E. & Stuermer, C. A., CNS myelin and oligodendrocytes of the Xenopus spinal cord — but not optic nerve — are nonpermissive for axon growth. J. Neurosci. 15, 99–109 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Dussault, J. H. & Ruel, J., Thyroid hormones and brain development. Annu. Rev. Physiol. 49, 321–334 (1987).

    Article  CAS  PubMed  Google Scholar 

  75. Barres, B. A., Lazar, M. A. & Raff, M. C., A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120, 1097–1108 (1994).

    Article  CAS  PubMed  Google Scholar 

  76. Fernandez, M., Pirondi, S., Manservigi, M., Giardino, L. & Calza, L., Thyroid hormone participates in the regulation of neural stem cells and oligodendrocyte precursor cells in the central nervous system of adult rat. Eur. J. Neurosci. 20, 2059–2070 (2004).

    Article  CAS  PubMed  Google Scholar 

  77. Zupanc, G. K., Adult neurogenesis and neuronal regeneration in the brain of teleost fish. J. Physiol. Paris 102, 357–373 (2008).

    Article  PubMed  Google Scholar 

  78. Margotta, V., Further amputations of the tail in adult Triturus carnifex: contribution to the study on the nature of regenerated spinal cord. Ital. J. Anat. Embryol. 113, 167–186 (2008).

    PubMed  Google Scholar 

  79. Margotta, V., Filoni, S., Merante, A. & Chimenti, C., Analysis of morphogenetic potential of caudal spinal cord in Triturus carnifex adults (Urodele amphibians) subjected to repeated tail amputations. Ital. J. Anat. Embryol. 107, 127–144 (2002).

    PubMed  Google Scholar 

  80. Nishino, J. & Morrison, S. J., Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell 135, 227–239 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yoshii, C., Ueda, Y., Okamoto, M. & Araki, M., Neural retinal regeneration in the anuran amphibian Xenopus laevis post-metamorphosis: transdifferentiation of retinal pigmented epithelium regenerates the neural retina. Dev. Biol. 303, 45–56 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Tsonis, P. A. & Eguchi, G., Carcinogens on regeneration. Effects of N-methyl-N′-nitro-N-nitrosoguanidine and 4-nitroquinoline-1-oxide on limb regeneration in adult newts. Differentiation 20, 52–60 (1981).

    Article  CAS  PubMed  Google Scholar 

  83. Dunlop, S. A. et al., Failure to restore vision after optic nerve regeneration in reptiles: interspecies variation in response to axotomy. J. Comp. Neurol. 478, 292–305 (2004).

    Article  PubMed  Google Scholar 

  84. Rodger, J. et al., Changing Pax6 expression correlates with axon outgrowth and restoration of topography during optic nerve regeneration. Neuroscience 142, 1043–1054 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Beazley, L. D. et al., Training on a visual task improves the outcome of optic nerve regeneration. J. Neurotrauma 20, 1263–1270 (2003).

    Article  CAS  PubMed  Google Scholar 

  86. Northcutt, R. G., Changing views of brain evolution. Brain Res. Bull. 55, 663–674 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Blackmore, M. & Letourneau, P. C., Changes within maturing neurons limit axonal regeneration in the developing spinal cord. J. Neurobiol. 66, 348–360 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Yamada, H., Miyake, T. & Kitamura, T., Regeneration of axons in transection of the carp spinal cord. Zool. Sci. 12, 325–332 (1995).

    Article  CAS  Google Scholar 

  89. Lurie, D. I. & Selzer, M. E., Preferential regeneration of spinal axons through the scar in hemisected lamprey spinal cord. J. Comp. Neurol. 313, 669–679 (1991).

    Article  CAS  PubMed  Google Scholar 

  90. Lang, D. M., Monzon-Mayor, M., Bandtlow, C. E. & Stuermer, C. A., Retinal axon regeneration in the lizard Gallotia galloti in the presence of CNS myelin and oligodendrocytes. Glia 23, 61–74 (1998).

    Article  CAS  PubMed  Google Scholar 

  91. Jacobs, A. J. et al., Recovery of neurofilament expression selectively in regenerating reticulospinal neurons. J. Neurosci. 17, 5206–5220 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Shifman, M. I., Zhang, G. & Selzer, M. E., Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys. J. Comp. Neurol. 510, 269–282 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Gillingwater, T. H. et al., Delayed synaptic degeneration in the CNS of Wlds mice after cortical lesion. Brain 129, 1546–1556 (2006).

    Article  PubMed  Google Scholar 

  94. Beirowski, B. et al., The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves. BMC Neurosci. 6, 6 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Hitchcock, P. F. & Raymond, P. A., Retinal regeneration. Trends Neurosci. 15, 103–108 (1992).

    Article  CAS  PubMed  Google Scholar 

  96. Mitashov, V. I., Mechanisms of retina regeneration in urodeles. Int. J. Dev. Biol. 40, 833–844 (1996).

    CAS  PubMed  Google Scholar 

  97. Lamba D, Karl M, Reh T. Neural regeneration and cell replacement: a view from the eye. Cell Stem Cell 2, 538–549 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Tsonis, P. A. & Del Rio-Tsonis, K., Lens and retina regeneration: transdifferentiation, stem cells and clinical applications. Exp. Eye Res. 78, 161–172 (2004).

    Article  CAS  PubMed  Google Scholar 

  99. Park, C. M. & Hollenberg, M. J., Induction of retinal regeneration in vivo by growth factors. Dev. Biol. 148, 322–333 (1991).

    Article  CAS  PubMed  Google Scholar 

  100. Sakami, S., Etter, P. & Reh, T. A., Activin signaling limits the competence for retinal regeneration from the pigmented epithelium. Mech. Dev. 125, 106–116 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Lledo, P. M., Alonso, M. & Grubb, M. S., Adult neurogenesis and functional plasticity in neuronal circuits. Nature Rev. Neurosci. 7, 179–193 (2006).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Y. Malashichev, V. Soukup and R. Voss for discussions on evolution. E.M.T. was supported by grants from the Deutsche Forschungsgemeinschaft: SFB655, SPP1356 and TA 274/3-1, and the Bundesministerium für Bildung und Forschung Biofutures. P.F. was suppported by grants from the Biotechnology and Biological Sciences Research Council and the Child Research Appeal Trust.

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  1. Center for Regeneration Therapies, University of Technology, Dresden, c/o Max-Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden, 01307, Germany

    Elly M. Tanaka

  2. Developmental Biology Unit, University College London Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Patrizia Ferretti

  3. Patrizia Ferretti

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Glossary

Metazoan

Any multicellular member of the animal kingdom.

Epiphenomenon

A by-product of another essential metazoan trait associated with development, tissue organization or asexual reproduction.

Blood–brain barrier

A barrier between the blood and the CNS, which is established by specialized capillaries and astrocytes and allows selective entry of compounds from the blood into the CNS parenchyma.

Glial scar

A barrier composed mainly of reactive astrocytes and proteoglycans that forms after CNS injury to separate healthy from damaged tissues.

Cellular automata

A method to simulate physical phenomena in space and time by using an array of units (cells) that have certain properties that change according to a given set of rules.

Melanophores

Pigment cells of neural crest origin that, during development, migrate from the neural tube to the skin and other pigmented tissues.

Taxon

The unit used in taxonomy (classification of plants and animals) to group related plants or animals together at any level of the hierarchy.

Paedomorphosis

A term describing the situation in which embryonic or juvenile characteristics of the ancestor are evident in an adult organism irrespective of the mechanism by which this state came about (encompasses neoteny).

Selfish junk DNA

DNA elements in the genome that were thought to have no functional role but to self-replicate and multiply within the host genome. Recent work suggests that this non-protein coding DNA contains important regulatory sequences.

Neotenic

A term describing a state whereby the development of a species' somatic body structures has slowed down or is absent, resulting in juvenile traits being present in an adult stage

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Tanaka, E., Ferretti, P. Considering the evolution of regeneration in the central nervous system. Nat Rev Neurosci 10, 713–723 (2009). https://doi.org/10.1038/nrn2707

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