A histological study of normal and pathological limb regeneration in the Mexican axolotl Ambystoma mexicanum.


Journal

Journal of experimental zoology. Part B, Molecular and developmental evolution
ISSN: 1552-5015
Titre abrégé: J Exp Zool B Mol Dev Evol
Pays: United States
ID NLM: 101168228

Informations de publication

Date de publication:
03 2021
Historique:
received: 10 10 2019
revised: 30 03 2020
accepted: 08 04 2020
pubmed: 13 5 2020
medline: 18 9 2021
entrez: 13 5 2020
Statut: ppublish

Résumé

Salamanders show unparalleled capacities of tissue regeneration amongst tetrapods (four-legged vertebrates), being able to repair and renew lost or damage body parts, such as tails, jaws, and limbs in a seemingly perfect fashion. Despite countless studies on axolotl (Ambystoma mexicanum) regeneration, only a few studies have thus far compared gross morphological and histological features of the original and regenerated limb skeleton. Therein, most studies have focused on nerves or muscles, while even fewer have provided detailed information about bones and cartilage. This study compares skeletal tissue structures of original and regenerated limbs with respect to tissue level histology. Histological serial sections of 55 axolotl larvae were generated, including 29 limbs that were severed by conspecifics, and 26 that were subject to targeted amputations. Amputations were executed in several larval stages (48, 52, and 53) and at different limb positions (humeral midshaft, above the mesopod). In addition, 3D reconstructions were prepared based on X-ray microtomography scans. The results demonstrate that regenerated forelimbs show a diversity of limb and digit abnormalities as a result of imperfect regeneration. Furthermore, abnormalities were more severe and more frequent in regenerated forelimbs caused by natural bites as compared with regenerated forelimbs after amputation. The results indicate that abnormalities occur frequently after regeneration in larval axolotls contradicting the notion of regeneration generally resulting in perfect limbs.

Identifiants

pubmed: 32394624
doi: 10.1002/jez.b.22950
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

116-128

Informations de copyright

© 2020 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals LLC.

Références

Allan, C. H., Fleckman, P., Fernandes, R. J., Hager, B., James, J., Wisecarver, Z., … Clark, J. M. (2006). Tissue response and Msx1 expression after human fetal digit tip amputation in vitro. Wound Repair and Regeneration, 14(4), 398-404.
Alvarado, A. S. (2000). Regeneration in the metazoans: Why does it happen? BioEssays, 22(6), 578-590.
Alvarado, A. S., & Tsonis, P. A. (2006). Bridging the regeneration gap: Genetic insights from diverse animal models. Nature Reviews Genetics, 7(11), 873-884.
Bely, A. E., & Nyberg, K. G. (2010). Evolution of animal regeneration: Re-emergence of a field. Trends in Ecology & Evolution, 25(3), 161-170.
de Both, N. J. (1970). The developmental potencies of the regeneration blastema of the axolotl limb. Wilhelm Roux'Archiv für Entwicklungsmechanik der Organismen, 165(3), 242-276.
Bowerman, J., Johnson, P. T., & Bowerman, T. (2010). Sublethal predators and their injured prey: Linking aquatic predators and severe limb abnormalities in amphibians. Ecology, 91(1), 242-251.
Brockes, J. P. (2015). Variation in salamanders: An essay on genomes, development and evolution. In A.Kumar & A.Simon (Eds.), Salamanders in regeneration research: methods and protocols (p. 357). New York, NY: Springer.
Brockes, J. P., & Gates, P. B. (2014). Mechanisms underlying vertebrate limb regeneration: Lessons from the salamander. Biochemical Society Transactions, 42(3), 625-630.
Bryant, D. M., Johnson, K., DiTommaso, T., Tickle, T., Couger, M. B., Payzin-Dogru, D., … Whited, J. L. (2017). A tissue-mapped axolotl de novo transcriptome enables identification of limb regeneration factors. Cell Reports, 18(3), 762-776.
Bryant, S. V., Endo, T., & Gardiner, D. M. (2002). Vertebrate limb regeneration and the origin of limb stem cells. International Journal of Developmental Biology, 46(7), 887-896.
Bryant, S. V., French, V., & Bryant, P. J. (1981). Distal regeneration and symmetry. Science, 212(4498), 993-1002.
Butler, E. G., & Schotte, O. E. (1941). Histological alterations in denervated non-regenerating limbs of urodele larvae. Journal of Experimental Zoology, 88(2), 307-341.
Carlson, B. M. (1967). The histology of inhibition of limb regeneration in the newt, Triturus, by actinomycin D. Journal of Morphology, 122(3), 249-263.
Carlson, M. R., Bryant, S. V., & Gardiner, D. M. (1998). Expression of Msx-2 during development, regeneration, and wound healing in axolotl limbs. Journal of Experimental Zoology, 282(6), 715-723.
Chen, X., Song, F., Jhamb, D., Li, J., Bottino, M. C., Palakal, M. J., & Stocum, D. L. (2015). The axolotl fibula as a model for the induction of regeneration across large segment defects in long bones of the extremities. PLoS One, 10(6):e0130819.
Contreras, V., Martínez-Meyer, E., Valiente, E., & Zambrano, L. (2009). Recent decline and potential distribution in the last remnant area of the microendemic Mexican axolotl (Ambystoma mexicanum). Biological Conservation, 142(12), 2881-2885.
Cosden, R. S., Lattermann, C., Romine, S., Gao, J., Voss, S. R., & MacLeod, J. N. (2011). Intrinsic repair of full-thickness articular cartilage defects in the axolotl salamander. Osteoarthritis and Cartilage, 19(2), 200-205.
Currie, J. D., Kawaguchi, A., Traspas, R. M., Schuez, M., Chara, O., & Tanaka, E. M. (2016). Live imaging of axolotl digit regeneration reveals spatiotemporal choreography of diverse connective tissue progenitor pools. Developmental Cell, 39(4), 411-423.
Darnet, S., Dragalzew, A. C., Amaral, D. B., Sousa, J. F., Thompson, A. W., Cass, A. N., Fröbisch, N. B., & Schneider, I. (2019). Deep evolutionary origin of limb and fin regeneration. Proceedings of the National Academy of Sciences of the United States of America, 116(30), 15106-15115.
Dearlove, G. E., & Dresden, M. H. (1976). Regenerative abnormalities in Notophthalmus viridescens induced by repeated amputations. Journal of Experimental Zoology, 196(2), 251-261.
Dinsmore, C. E. (1991). A history of regeneration research: Milestones in the evolution of a science, Cambridge, UK: Cambridge University Press.
Dinsmore, C. E., & Hanken, J. (1986). Native variant limb skeletal patterns in the red-backed salamander, Plethodon cinereus, are not regenerated. Journal of Morphology, 190(2), 191-200.
Diogo, R., Murawala, P., & Tanaka, E. M. (2014). Is salamander hindlimb regeneration similar to that of the forelimb? Anatomical and morphogenetic analysis of hindlimb muscle regeneration in GFP-transgenic axolotls as a basis for regenerative and developmental studies. Journal of Anatomy, 224(4), 459-468.
Diogo, R., Nacu, E., & Tanaka, E. M. (2014). Is salamander limb regeneration really perfect? Anatomical and morphogenetic analysis of forelimb muscle regeneration in GFP-transgenic axolotls as a basis for regenerative, developmental, and evolutionary studies. The Anatomical Record, 297(6), 1076-1089.
Diogo, R., & Tanaka, E. M. (2014). Development of fore-and hindlimb muscles in GFP-transgenic axolotls: Morphogenesis, the tetrapod bauplan, and new insights on the Forelimb-Hindlimb Enigma. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 322(2), 106-127.
Dunis, D. A., & Namenwirth, M. (1977). The role of grafted skin in the regeneration of x-irradiated axolotl limbs. Developmental Biology, 56(1), 97-109.
Echeverri, K., & Tanaka, E. M. (2002). Ectoderm to mesoderm lineage switching during axolotl tail regeneration. Science, 298(5600), 1993-1996.
Echeverri, K., & Tanaka, E. M. (2005). Proximodistal patterning during limb regeneration. Developmental Biology, 279(2), 391-401.
Ferguson, M. W., & O'Kane, S. (2004). Scar-free healing: From embryonic mechanisms to adult therapeutic intervention. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 359(1445), 839-850.
Forsyth, J. W. (1946). The histology of anuran limb regeneration. Journal of Morphology, 79(2), 287-321.
French, V., Bryant, P. J., & Bryant, S. V. (1976). Pattern regulation in epimorphic fields. Science, 193(4257), 969-981.
Fröbisch, N. B., Bickelmann, C., Olori, J. C., & Witzmann, F. (2015). Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development. Nature, 527(7577), 231-234.
Fröbisch, N. B., Bickelmann, C., & Witzmann, F. (2014). Early evolution of limb regeneration in tetrapods: Evidence from a 300-million-year-old amphibian. Proceedings of the Royal Society of London B: Biological Sciences, 281(1794):20141550.
Gamradt, S. C., & Kats, L. B. (1996). Effect of introduced crayfish and mosquitofish on California newts. Conservation Biology, 10, 1155-1162.
Gardiner, D. M., Blumberg, B., Komine, Y., & Bryant, S. V. (1995). Regulation of HoxA expression in developing and regenerating axolotl limbs. Development, 121(6), 1731-1741.
Gardiner, D. M., & Bryant, S. V. (2007). Tetrapod limb regeneration, Fins into limbs: Evolution, development, and transformation (pp. 163-182). Chicago, IL: University of Chicago Press.
Gassner, K. M., & Tassava, R. A. (1997). Abnormal limb regeneration in the short-toes mutant of the axolotl, Ambystoma mexicanum: Studies of age, level of amputation, and extracellular matrix. Journal of Experimental Zoology Part A: Ecological Genetics and Physiology, 279(6), 571-578.
Gerber, T., Murawala, P., Knapp, D., Masselink, W., Schuez, M., Hermann, S., … Treutlein, B. (2018). Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration. Science, 362(6413):eaaq0681.
Goss, R. J. (1969). Principles of regeneration. Academic Press, London, 278.
Ghosh, S., Thorogood, P., & Ferretti, P. (1994). Regenerative capability of upper and lower jaws in the newt. The International Journal of Developmental Biology, 38(3), 479-490.
Godwin, J. W., & Rosenthal, N. (2014). Scar-free wound healing and regeneration in amphibians: Immunological influences on regenerative success. Differentiation, 87(1), 66-75.
Goss, R. J. (1956). The relation of bone to the histogenesis of cartilage in regenerating forelimbs and tails of adult Triturus viridescens. Journal of Morphology, 98(1), 89-123.
Graue, V., Sánchez-Robles, J., Castro, G., Caumatzi, O., Márquez, Y., & Vázquez, M. (1998). Breeding the axolotl in its native habitat. Axolotl Newsletter, 27, 4-6.
Grim, M., & Carlson, B. M. (1974). A comparison of morphogenesis of muscles of the forearm and hand during ontogenesis and regeneration in the axolotl (Ambystoma mexicanum). Zeitschrift für Anatomie und Entwicklungsgeschichte, 145(2), 149-167.
Gupta, S. (2016). Animal models: Unlock your inner salamander. Nature, 540(7632), S58-S59.
Han, M., Yang, X., Farrington, J. E., & Muneoka, K. (2003). Digit regeneration is regulated by Msx1 and BMP4 in fetal mice. Development, 130(21), 5123-5132.
Hutchison, C., Pilote, M., & Roy, S. (2007). The axolotl limb: A model for bone development, regeneration and fracture healing. Bone, 40(1), 45-56.
Johnson, P. T., Preu, E. R., Sutherland, D. R., Romansic, J. M., Han, B., & Blaustein, A. R. (2006). Adding infection to injury: Synergistic effects of predation and parasitism on amphibian malformations. Ecology, 87(9), 2227-2235.
Kragl, M., Knapp, D., Nacu, E., Khattak, S., Maden, M., Epperlein, H. H., & Tanaka, E. M. (2009). Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature, 460(7251), 60-65.
Kumar, A., Gates, P. B., Czarkwiani, A., & Brockes, J. P. (2015). An orphan gene is necessary for preaxial digit formation during salamander limb development. Nature Communications, 6, 8684.
Lee, J., & Gardiner, D. M. (2012). Regeneration of limb joints in the axolotl (Ambystoma mexicanum). Plos One, 7(11):e50615.
Lenhoff, H. M., & Lenhoff, S. G. (1991). Abraham Trembley and the origins of research on regeneration in animals. In C. E.Dinsmore (Ed.), A history of regeneration research: Milestones in the evolution of a science (pp. 47-66). Cambridge, UK: Cambridge University Press.
Lévesque, M., Villiard, É., & Roy, S. (2010). Skin wound healing in axolotls: A scarless process. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 314(8), 684-697.
Maden, M., & Goodwin, B. C. (1980). Experiments on developing limb buds of the axolotl Ambystoma mexicanum. Journal of Embryology and Experimental Morphology, 57(1), 177-187.
McCusker, C. D., & Gardiner, D. M. (2013). Positional information is reprogrammed in blastema cells of the regenerating limb of the axolotl (Ambystoma mexicanum). PLoS One, 8(9):e77064.
McCusker, C. D., Lehrberg, J., & Gardiner, D. (2014). Position-specific induction of ectopic limbs in non-regenerating blastemas on axolotl forelimbs. Regeneration, 1(1), 27-34.
Mercader, N., Tanaka, E. M., & Torres, M. (2005). Proximodistal identity during vertebrate limb regeneration is regulated by Meis homeodomain proteins. Development, 132(18), 4131-4142.
Mescher, A. L. (1996). The cellular basis of limb regeneration in urodeles. International Journal of Developmental Biology, 40, 785-795.
Metscher, B. D. (2009). MicroCT for comparative morphology: Simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues. BMC Physiology, 9(1), 11.
Mitashov, V. I. (1996). Mechanisms of retina regeneration in urodeles. International Journal of Developmental Biology, 40, 833-844.
Morgan, T. H. (1898). Experimental studies of the regeneration of Planaria maculata. Development Genes and Evolution, 7(2), 364-397.
Nogueira, A. F., Costa, C. M., Lorena, J., Moreira, R. N., Frota-Lima, G. N., Furtado, C., … Schneider, I. (2016). Tetrapod limb and sarcopterygian fin regeneration share a core genetic programme. Nature Communications, 7, 13364.
Nye, H. L., Cameron, J. A., Chernoff, E. A., & Stocum, D. L. (2003a). Extending the table of stages of normal development of the axolotl: Limb development. Developmental Dynamics, 226(3), 555-560.
Nye, H. L., Cameron, J. A., Chernoff, E. A., & Stocum, D. L. (2003b). Regeneration of the urodele limb: A review. Developmental Dynamics, 226(2), 280-294.
Oberpriller, J. O., & Oberpriller, J. C. (1974). Response of the adult newt ventricle to injury. Journal of Experimental Zoology, 187(2), 249-259.
Piatt, J. (1957). Studies on the problem of nerve pattern. III. Innervation of the regenerated forelimb in Amblystoma. Journal of Experimental Zoology, 136(2), 229-247.
Reiß, C., Olsson, L., & Hoßfeld, U. W. E. (2015). The history of the oldest self-sustaining laboratory animal: 150 years of axolotl research. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 324(5), 393-404.
Reyer, R. W. (1954). Regeneration of the lens in the amphibian eye. Quarterly Review of Biology, 29, 1-46.
Roensch, K., Tazaki, A., Chara, O., & Tanaka, E. M. (2013). Progressive specification rather than intercalation of segments during limb regeneration. Science, 342(6164), 1375-1379.
Roy, S., & Gatien, S. (2008). Regeneration in axolotls: A model to aim for!Experimental Gerontology, 43(11), 968-973.
Roy, S., & Lévesque, M. (2006). Limb regeneration in axolotl: Is it superhealing? The Scientific World Journal, 6, 12-25.
Satoh, A., Bryant, S. V., & Gardiner, D. M. (2008). Regulation of dermal fibroblast dedifferentiation and redifferentiation during wound healing and limb regeneration in the Axolotl. Development, Growth & Differentiation, 50(9), 743-754.
Semlitsch, R. D., & Reichling, S. B. (1989). Density-dependent injury in larval salamanders. Oecologia, 81(1), 100-103.
Shaw, G., & Nodder, F. P. (1798). The Naturalist's Miscellany; or Coloured Figures of Natural Objects Drawn and Described Immediately from Nature, 9. London.
Shubin, N., Wake, D. B., & Crawford, A. J. (1995). Morphological variation in the limbs of Taricha granulosa (Caudata: Salamandridae): Evolutionary and phylogenetic implications. Evolution, 49(5), 874-884.
Simon, A., & Tanaka, E. M. (2013). Limb regeneration. Wiley Interdisciplinary Reviews: Developmental Biology, 2, 291-300.
Spallanzani, L. (1768). Prodromo di un'opera da imprimersi sopra le riproduzioni animali. Modena, Italy: Nella Stamperia di Giovanni Montanari.
Stephens, N., & Holder, N. (1987). Reformation of the pattern of neuromuscular connections in the regenerated axolotl hindlimb. Development, 99(2), 221-230.
Stock, G. B., & Bryant, S. V. (1981). Studies of digit regeneration and their implications for theories of development and evolution of vertebrate limbs. Journal of Experimental Zoology Part A: Ecological Genetics and Physiology, 216(3), 423-433.
Stock, S. R., Blackburn, D., Gradassi, M., & Simon, H. G. (2003). Bone formation during forelimb regeneration: A microtomography (microCT) analysis. Developmental Dynamics, 226(2), 410-417.
Stocum, D. L. (1979). Stages of forelimb regeneration in Ambystoma maculatum. Journal of Experimental Zoology, 209(3), 395-416.
Tanaka, E. M. (2003). Regeneration: If they can do it, why can't we? Cell, 113(5), 559-562.
Tanaka, E. M. (2016). The molecular and cellular choreography of appendage regeneration. Cell, 165(7), 1598-1608.
Tank, P. W., Carlson, B. M., & Connelly, T. G. (1976). A staging system for forelimb regeneration in the axolotl, Ambystoma mexicanum. Journal of Morphology, 150(1), 117-128.
Thompson, S., Muzinic, L., Muzinic, C., Niemiller, M. L., & Voss, S. R. (2014). Probability of regenerating a normal limb after bite injury in the Mexican axolotl (Ambystoma mexicanum). Regeneration, 1(3), 27-32.
Thornton, C. S. (1938). The histogenesis of muscle in the regenerating fore limb of larval Amblystoma punctatum. Journal of Morphology, 62(1), 17-47.
Torok, M. A., Gardiner, D. M., Shubin, N. H., & Bryant, S. V. (1998). Expression of HoxD genes in developing and regenerating axolotl limbs. Developmental Biology, 200(2), 225-233.
Tsonis, P. A. (2000). Regeneration in vertebrates. Developmental Biology, 221(2), 273-284.
Walls, S. C., & Jaeger, R. G. (1987). Aggression and exploitation as mechanisms of competition in larval salamanders. Canadian Journal of Zoology, 65(12), 2938-2944.
Weiss, P., & Walker, R. (1934). Nerve pattern in regenerated urodele limbs. Experimental Biology and Medicine, 31(7), 810-812.
Wildy, E. L., Chivers, D. P., Kiesecker, J. M., & Blaustein, A. R. (2001). The effects of food level and conspecific density on biting and cannibalism in larval long-toed salamanders, Ambystoma macrodactylum. Oecologia, 128(2), 202-209.
Young, H. E. (1977). Anomalies of limb regeneration in the adult salamander Ambystoma annulatum. Proceedings of the Arkansas Academy of Science, 31, 110-111.
Zambrano, L., Contreras, V., Mazari-Hiriart, M., & Zarco-Arista, A. E. (2009). Spatial heterogeneity of water quality in a highly degraded tropical freshwater ecosystem. Environmental Management, 43(2), 249-263.
Zambrano, L., Vega, E., Herrera, M., Prado, E., & Reynoso, V. H. (2007). A population matrix model and population viability analysis to predict the fate of endangered species in highly managed water systems. Animal Conservation, 10(3), 297-303.
Zeleny, C. (1909). The relation between degree of injury and rate of regeneration-additional observations and general discussion. Journal of Experimental Zoology, 7(3), 513-561.

Auteurs

Vivien Bothe (V)

Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany.

Kristin Mahlow (K)

Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany.

Nadia B Fröbisch (NB)

Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany.
Humboldt-Universität zu Berlin, Berlin, Germany.

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