Abstract
Despite current treatment regimens, heart failure still remains one of the leading causes of morbidity and mortality in the world due to failure to adequately replace lost ventricular myocardium from ischemia-induced infarct. Although adult mammalian ventricular cardiomyocytes have a limited capacity to divide, this proliferation is insufficient to overcome the significant loss of myocardium from ventricular injury. However, lower vertebrates, such as the zebrafish and newt, have the remarkable capacity to fully regenerate their hearts after severe injury. Thus, there is great interest in studying these animal model systems to discover new regenerative approaches that might be applied to injured mammalian hearts. To this end, the zebrafish has been utilized more recently to gain additional mechanistic insight into cardiac regeneration because of its genetic tractability. Here, we describe two cardiac injury methods, a mechanical and a genetic injury model, for studying cardiac regeneration in the zebrafish.
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References
Hsieh PC, Segers VF, Davis ME, MacGillivray C, Gannon J, Molkentin JD, Robbins J, Lee RT (2007) Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 13:970–974
Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102
Bersell K, Arab S, Haring B, Kuhn B (2009) Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 138:257–270
Major RJ, Poss KD (2007) Zebrafish heart regeneration as a model for cardiac tissue repair. Drug Discov Today Dis Models 4:219–225
Mochii M, Taniguchi Y, Shikata I (2007) Tail regeneration in the Xenopus tadpole. Dev Growth Differ 49:155–161
Lin G, Chen Y, Slack JM (2007) Regeneration of neural crest derivatives in the Xenopus tadpole tail. BMC Dev Biol 7:56
Oberpriller JO, Oberpriller JC, Aafedt BC (1987) Changes in binucleation and cellular dimensions of rat left atrial myocytes after induced left ventricular infarction. Am J Anat 179:285–290
Oberpriller JO, Oberpriller JC (1974) Response of the adult newt ventricle to injury. J Exp Zool 187:249–253
Flink IL (2002) Cell cycle reentry of ventricular and atrial cardiomyocytes and cells within the epicardium following amputation of the ventricular apex in the axolotl, Amblystoma mexicanum: confocal microscopic immunofluorescent image analysis of bromodeoxyuridine-labeled nuclei. Anat Embryol (Berl) 205:235–244
Endo T, Yoshino J, Kado K, Tochinai S (2007) Brain regeneration in anuran amphibians. Dev Growth Differ 49:121–129
Mescher AL, Neff AW (2006) Limb regeneration in amphibians: immunological considerations. ScientificWorldJournal 6(Suppl 1):1–11
Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM (2009) Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460:60–65
Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190
Lepilina A, Coon AN, Kikuchi K, Holdway JE, Roberts RW, Burns CG, Poss KD (2006) A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 127:607–619
Poss KD (2007) Getting to the heart of regeneration in zebrafish. Semin Cell Dev Biol 18:36–45
Poss KD, Shen J, Nechiporuk A, McMahon G, Thisse B, Thisse C, Keating MT (2000) Roles for Fgf signaling during zebrafish fin regeneration. Dev Biol 222:347–358
Jopling C, Sleep E, Raya M, Marti M, Raya A, Belmonte JC (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609
Kikuchi K, Holdway JE, Werdich AA, Anderson RM, Fang Y, Egnaczyk GF, Evans T, Macrae CA, Stainier DY, Poss KD (2010) Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature 464:601–605
Gonzalez-Rosa JM, Martin V, Peralta M, Torres M, Mercader N (2011) Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish. Development 138:1663–1674
Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080
Lien CL, Schebesta M, Makino S, Weber GJ, Keating MT (2006) Gene expression analysis of zebrafish heart regeneration. PLoS Biol 4:e260
Robey TE, Murry CE (2008) Absence of regeneration in the MRL/MpJ mouse heart following infarction or cryoinjury. Cardiovasc Pathol 17:6–13
Wang J, Panakova D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, Singh SP, Dickson AL, Lin YF, Sabeh MK, Werdich AA, Yelon D, Macrae CA, Poss KD (2011) The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development 138:3421–3430
Akazawa H, Komazaki S, Shimomura H, Terasaki F, Zou Y, Takano H, Nagai T, Komuro I (2004) Diphtheria toxin-induced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure. J Biol Chem 279:41095–41103
Breitman ML, Clapoff S, Rossant J, Tsui LC, Glode LM, Maxwell IH, Bernstein A (1987) Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice. Science 238:1563–1565
Brockschnieder D, Lappe-Siefke C, Goebbels S, Boesl MR, Nave KA, Riethmacher D (2004) Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination. Mol Cell Biol 24:7636–7642
Lee P, Morley G, Huang Q, Fischer A, Seiler S, Horner JW, Factor S, Vaidya D, Jalife J, Fishman GI (1998) Conditional lineage ablation to model human diseases. Proc Natl Acad Sci USA 95:11371–11376
Saito M, Iwawaki T, Taya C, Yonekawa H, Noda M, Inui Y, Mekada E, Kimata Y, Tsuru A, Kohno K (2001) Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat Biotechnol 19:746–750
Stanger BZ, Tanaka AJ, Melton DA (2007) Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445:886–891
Curado S, Anderson RM, Jungblut B, Mumm J, Schroeter E, Stainier DY (2007) Conditional targeted cell ablation in zebrafish: a new tool for regeneration studies. Dev Dyn 236:1025–1035
Medico E, Gambarotta G, Gentile A, Comoglio PM, Soriano P (2001) A gene trap vector system for identifying transcriptionally responsive genes. Nat Biotechnol 19:579–582
Pisharath H, Rhee JM, Swanson MA, Leach SD, Parsons MJ (2007) Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductase. Mech Dev 124:218–229
Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473:326–335
Davison JM, Akitake CM, Goll MG, Rhee JM, Gosse N, Baier H, Halpern ME, Leach SD, Parsons MJ (2007) Transactivation from Gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafish. Dev Biol 304:811–824
Anderson RM, Bosch JA, Goll MG, Hesselson D, Dong PD, Shin D, Chi NC, Shin CH, Schlegel A, Halpern M, Stainier DY (2009) Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration. Dev Biol 334:213–223
Beis D, Stainier DY (2006) In vivo cell biology: following the zebrafish trend. Trends Cell Biol 16:105–112
Stoick-Cooper CL, Weidinger G, Riehle KJ, Hubbert C, Major MB, Fausto N, Moon RT (2007) Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development 134:479–489
Jin SW, Beis D, Mitchell T, Chen JN, Stainier DY (2005) Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development 132:5199–5209
de Pater E, Clijsters L, Marques SR, Lin YF, Garavito-Aguilar ZV, Yelon D, Bakkers J (2009) Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish heart. Development 136:1633–1641
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Dickover, M.S., Zhang, R., Han, P., Chi, N.C. (2013). Zebrafish Cardiac Injury and Regeneration Models: A Noninvasive and Invasive In Vivo Model of Cardiac Regeneration. In: Gourdie, R., Myers, T. (eds) Wound Regeneration and Repair. Methods in Molecular Biology, vol 1037. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-505-7_27
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DOI: https://doi.org/10.1007/978-1-62703-505-7_27
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