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Science 310 (5756): 1919-1923

Copyright © 2005 by the American Association for the Advancement of Science

Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine

Jeremy P. Brockes*, and Anoop Kumar

Abstract: The regeneration of complex structures in adult salamanders depends on mechanisms that offer pointers for regenerative medicine. These include the plasticity of differentiated cells and the retention in regenerative cells of local cues such as positional identity. Limb regeneration proceeds by the local formation of a blastema, a growth zone of mesenchymal stem cells on the stump. The blastema can regenerate autonomously as a self-organizing system over variable linear dimensions. Here we consider the prospects for limb regeneration in mammals from this viewpoint.

Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.

* To whom correspondence should be addressed. E-mail: j.brockes{at}

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   Abstract »    Full Text »    PDF »
Macrophages are required for adult salamander limb regeneration.
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PNAS 110, 9415-9420
   Abstract »    Full Text »    PDF »
Keratin gene expression profiles after digit amputation in C57BL/6 vs. regenerative MRL mice imply an early regenerative keratinocyte activated-like state.
C.-H. Cheng, J. Leferovich, X.-M. Zhang, K. Bedelbaeva, D. Gourevitch, C. J. Hatcher, C. T. Basson, E. Heber-Katz, and K. A. Marx (2013)
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Development 140, 1137-1146
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Migration of cardiomyocytes is essential for heart regeneration in zebrafish.
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Development 139, 4133-4142
   Abstract »    Full Text »    PDF »
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PNAS 109, 13662-13667
   Abstract »    Full Text »    PDF »
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J. Neurosci. 31, 7876-7885
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Functional convergence of signalling by GPI-anchored and anchorless forms of a salamander protein implicated in limb regeneration.
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   Abstract »    Full Text »    PDF »
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Am J Physiol Cell Physiol 300, C1-C5
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Integr. Comp. Biol. 50, 528-535
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Ras controls melanocyte expansion during zebrafish fin stripe regeneration.
Y. Lee, G. Nachtrab, P. W. Klinsawat, D. Hami, and K. D. Poss (2010)
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Myc Function in Drosophila.
P. Bellosta and P. Gallant (2010)
Genes & Cancer 1, 542-546
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Lack of p21 expression links cell cycle control and appendage regeneration in mice.
K. Bedelbaeva, A. Snyder, D. Gourevitch, L. Clark, X.-M. Zhang, J. Leferovich, J. M. Cheverud, P. Lieberman, and E. Heber-Katz (2010)
PNAS 107, 5845-5850
   Abstract »    Full Text »    PDF »
IGF signaling between blastema and wound epidermis is required for fin regeneration.
F. Chablais and A. Jazwinska (2010)
Development 137, 871-879
   Abstract »    Full Text »    PDF »
Plasticity and recovery of skeletal muscle satellite cells during limb regeneration.
J. I. Morrison, P. Borg, and A. Simon (2010)
FASEB J 24, 750-756
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BMP signaling induces digit regeneration in neonatal mice.
L. Yu, M. Han, M. Yan, E.-C. Lee, J. Lee, and K. Muneoka (2010)
Development 137, 551-559
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Phil Trans R Soc B 365, 155-163
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A histone demethylase is necessary for regeneration in zebrafish.
S. Stewart, Z.-Y. Tsun, and J. C. I. Belmonte (2009)
PNAS 106, 19889-19894
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MafB/c-Maf Deficiency Enables Self-Renewal of Differentiated Functional Macrophages.
A. Aziz, E. Soucie, S. Sarrazin, and M. H. Sieweke (2009)
Science 326, 867-871
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Fully functional bioengineered tooth replacement as an organ replacement therapy.
E. Ikeda, R. Morita, K. Nakao, K. Ishida, T. Nakamura, T. Takano-Yamamoto, M. Ogawa, M. Mizuno, S. Kasugai, and T. Tsuji (2009)
PNAS 106, 13475-13480
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Manipulating myocyte cell cycle control for cardiac repair.
T. A. Gorr and A. Deten (2008)
Cardiovasc Res 80, 161-162
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Avotermin: A Novel Antiscarring Agent.
P. Durani, N. Occleston, S. O'Kane, and M. W. J. Ferguson (2008)
International Journal of Lower Extremity Wounds 7, 160-168
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D. C Blackburn, J. Hanken, and F. A Jenkins Jr (2008)
Biol Lett 4, 355-357
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Phil Trans R Soc B 363, 9-22
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J. Biol. Chem. 282, 35202-35210
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Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate.
A. Kumar, J. W. Godwin, P. B. Gates, A. A. Garza-Garcia, and J. P. Brockes (2007)
Science 318, 772-777
   Abstract »    Full Text »    PDF »
Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model.
C. L. Parish, A. Beljajeva, E. Arenas, and A. Simon (2007)
Development 134, 2881-2887
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Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration.
A. D Metcalfe and M. W.J Ferguson (2007)
J R Soc Interface 4, 413-437
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Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration.
P. Ahuja, P. Sdek, and W. R. MacLellan (2007)
Physiol Rev 87, 521-544
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Wnt/beta-catenin signaling regulates vertebrate limb regeneration.
Y. Kawakami, C. Rodriguez Esteban, M. Raya, H. Kawakami, M. Marti, I. Dubova, and J. C. Izpisua Belmonte (2006)
Genes & Dev. 20, 3232-3237
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Regrow or Repair: Potential Regenerative Therapies for the Kidney.
M. H. Little (2006)
J. Am. Soc. Nephrol. 17, 2390-2401
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