Abstract
Heart failure caused by cardiomyocyte loss after ischemic tissue damage is a leading cause of death worldwide, since adult mammals cannot regenerate heart injuries. While some new cardiomyocytes are produced in adult mammals during normal ageing and after infarction, this occurs at insufficient rates for effective cardiac regeneration. Zebrafish, on the contrary, are able to regenerate multiple organs including the heart. Injuries induce complex cellular and molecular responses in endocardium, epicardium and myocardium, which robustly regenerate in a coordinated manner, resulting in full morphological and functional recovery. In particular, differentiated cardiomyocytes re-enter the cell cycle and proliferate to regenerate the myocardium. Thus, the zebrafish has emerged as an important model to study mechanisms of naturally occurring cardiac regeneration. Here, we describe zebrafish heart injury techniques and review current data on mammalian cardiomyocyte turnover and production in response to injury as well as our current knowledge of the cellular and molecular mechanisms of zebrafish heart regeneration.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aguirre A, Montserrat N, Zacchigna S, Nivet E, Hishida T, Krause MN, Kurian L, Ocampo A, Vazquez-Ferrer E, Rodriguez-Esteban C, Kumar S, Moresco JJ, Yates JR 3rd, Campistol JM, Sancho-Martinez I, Giacca M, Izpisua Belmonte JC (2014) In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell 15(5):589–604. doi:10.1016/j.stem.2014.10.003
Ali SR, Hippenmeyer S, Saadat LV, Luo L, Weissman IL, Ardehali R (2014) Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice. Proc Natl Acad Sci U S A 111(24):8850–8855. doi:10.1073/pnas.1408233111
Belousov VV, Fradkov AF, Lukyanov KA, Staroverov DB, Shakhbazov KS, Terskikh AV, Lukyanov S (2006) Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat Methods 3(4):281–286. doi:10.1038/nmeth866
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(5923):98–102. doi:10.1126/science.1164680
Bersell K, Arab S, Haring B, Kuhn B (2009) Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 138(2):257–270. doi:10.1016/j.cell.2009.04.060
Beauchemin M, Smith A, Yin VP (2015) Dynamic microRNA-101a and Fosab expression controls zebrafish heart regeneration. Development 142(23):4026–4037. doi:10.1242/dev.126649
Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X, Stallcup WB, Denton CP, McCulloch A, Chen J, Evans SM (2008) A myocardial lineage derives from Tbx18 epicardial cells. Nature 454(7200):104–108. doi:10.1038/nature06969
Chablais F, Jazwinska A (2012) The regenerative capacity of the zebrafish heart is dependent on TGFbeta signaling. Development 139(11):1921–1930. doi:10.1242/dev.078543
Chablais F, Veit J, Rainer G, Jazwinska A (2011) The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 11:21. doi:10.1186/1471-213X-11-21
Chan DW, Liu VW, Tsao GS, Yao KM, Furukawa T, Chan KK, Ngan HY (2008) Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells. Carcinogenesis 29(9):1742–1750. doi:10.1093/carcin/bgn167
Choi WY, Gemberling M, Wang J, Holdway JE, Shen MC, Karlstrom RO, Poss KD (2013) In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development 140(3):660–666. doi:10.1242/dev.088526
D’Uva G, Aharonov A, Lauriola M, Kain D, Yahalom-Ronen Y, Carvalho S, Weisinger K, Bassat E, Rajchman D, Yifa O, Lysenko M, Konfino T, Hegesh J, Brenner O, Neeman M, Yarden Y, Leor J, Sarig R, Harvey RP, Tzahor E (2015) ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nat Cell Biol. doi:10.1038/ncb3149
Dettman RW, Denetclaw W Jr, Ordahl CP, Bristow J (1998) Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 193(2):169–181. doi:10.1006/dbio.1997.8801
Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, Henning BJ, Stirparo GG, Papait R, Scarfo M, Agosti V, Viglietto G, Condorelli G, Indolfi C, Ottolenghi S, Torella D, Nadal-Ginard B (2013) Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell 154(4):827–842. doi:10.1016/j.cell.2013.07.039
Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT (2005) p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev 19(10):1175–1187. doi:10.1101/gad.1306705
Engel FB, Hsieh PC, Lee RT, Keating MT (2006) FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. Proc Natl Acad Sci U S A 103(42):15546–15551. doi:10.1073/pnas.0607382103
Eulalio A, Mano M, Dal Ferro M, Zentilin L, Sinagra G, Zacchigna S, Giacca M (2012) Functional screening identifies miRNAs inducing cardiac regeneration. Nature 492(7429):376–381. doi:10.1038/nature11739
Fang Y, Gupta V, Karra R, Holdway JE, Kikuchi K, Poss KD (2013) Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration. Proc Natl Acad Sci U S A 110(33):13416–13421. doi:10.1073/pnas.1309810110
Gauron C, Rampon C, Bouzaffour M, Ipendey E, Teillon J, Volovitch M, Vriz S (2013) Sustained production of ROS triggers compensatory proliferation and is required for regeneration to proceed. Sci Rep 3:2084. doi:10.1038/srep02084
Gemberling M, Bailey TJ, Hyde DR, Poss KD (2013) The zebrafish as a model for complex tissue regeneration. Trends Genet 29(11):611–620. doi:10.1016/j.tig.2013.07.003
Gemberling M, Karra R, Dickson AL, Poss KD (2015) Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish. eLife 4:e05871. doi:10.7554/eLife.05871
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(9):1663–1674. doi:10.1242/dev.060897
Gonzalez-Rosa JM, Peralta M, Mercader N (2012) Pan-epicardial lineage tracing reveals that epicardium derived cells give rise to myofibroblasts and perivascular cells during zebrafish heart regeneration. Dev Biol 370(2):173–186. doi:10.1016/j.ydbio.2012.07.007
Gonzalez-Rosa JM, Guzman-Martinez G, Marques IJ, Sanchez-Iranzo H, Jimenez-Borreguero LJ, Mercader N (2014) Use of echocardiography reveals reestablishment of ventricular pumping efficiency and partial ventricular wall motion recovery upon ventricular cryoinjury in the zebrafish. PLoS One 9(12):e115604. doi:10.1371/journal.pone.0115604
Gupta V, Poss KD (2012) Clonally dominant cardiomyocytes direct heart morphogenesis. Nature 484(7395):479–484. doi:10.1038/nature11045
Gupta V, Gemberling M, Karra R, Rosenfeld GE, Evans T, Poss KD (2013) An injury-responsive gata4 program shapes the zebrafish cardiac ventricle. Curr Biol 23(13):1221–1227. doi:10.1016/j.cub.2013.05.028
Han P, Zhou XH, Chang N, Xiao CL, Yan S, Ren H, Yang XZ, Zhang ML, Wu Q, Tang B, Diao JP, Zhu X, Zhang C, Li CY, Cheng H, Xiong JW (2014) Hydrogen peroxide primes heart regeneration with a derepression mechanism. Cell Res 24(9):1091–1107. doi:10.1038/cr.2014.108
Heallen T, Morikawa Y, Leach J, Tao G, Willerson JT, Johnson RL, Martin JF (2013) Hippo signaling impedes adult heart regeneration. Development 140(23):4683–4690. doi:10.1242/dev.102798
Hein SJ, Lehmann LH, Kossack M, Juergensen L, Fuchs D, Katus HA, Hassel D (2015) Advanced echocardiography in adult zebrafish reveals delayed recovery of heart function after myocardial cryoinjury. PLoS One 10(4):e0122665. doi:10.1371/journal.pone.0122665
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(8):970–974. doi:10.1038/nm1618
Hu N, Yost HJ, Clark EB (2001) Cardiac morphology and blood pressure in the adult zebrafish. Anat Rec 264(1):1–12
Huang Y, Harrison MR, Osorio A, Kim J, Baugh A, Duan C, Sucov HM, Lien CL (2013) Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration. PLoS One 8(6):e67266. doi:10.1371/journal.pone.0067266
Huang CC, Su TH, Shih CC (2015) High-resolution tissue Doppler imaging of the zebrafish heart during its regeneration. Zebrafish 12(1):48–57. doi:10.1089/zeb.2014.1026
Ito K, Morioka M, Kimura S, Tasaki M, Inohaya K, Kudo A (2014) Differential reparative phenotypes between zebrafish and medaka after cardiac injury. Dev Dyn 243(9):1106–1115. doi:10.1002/dvdy.24154
Itou J, Oishi I, Kawakami H, Glass TJ, Richter J, Johnson A, Lund TC, Kawakami Y (2012) Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Development 139(22):4133–4142. doi:10.1242/dev.079756
Jopling C, Sleep E, Raya M, Marti M, Raya A, Izpisua Belmonte JC (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464(7288):606–609. doi:10.1038/nature08899
Jopling C, Sune G, Faucherre A, Fabregat C, Izpisua Belmonte JC (2012a) Hypoxia induces myocardial regeneration in zebrafish. Circulation 126(25):3017–3027. doi:10.1161/CIRCULATIONAHA.112.107888
Jopling C, Sune G, Morera C, Izpisua Belmonte JC (2012b) p38alpha MAPK regulates myocardial regeneration in zebrafish. Cell Cycle 11(6):1195–1201. doi:10.4161/cc.11.6.19637
Kang BJ, Park J, Kim J, Kim HH, Lee C, Hwang JY, Lien CL, Shung KK (2015) High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts. J R Soc Interface 12(103). doi:10.1098/rsif.2014.1154
Karra R, Knecht AK, Kikuchi K, Poss KD (2015) Myocardial NF-kappaB activation is essential for zebrafish heart regeneration. Proc Natl Acad Sci U S A 112(43):13255–13260. doi:10.1073/pnas.1511209112
Kido M, Du L, Sullivan CC, Li X, Deutsch R, Jamieson SW, Thistlethwaite PA (2005) Hypoxia-inducible factor 1-alpha reduces infarction and attenuates progression of cardiac dysfunction after myocardial infarction in the mouse. J Am Coll Cardiol 46(11):2116–2124. doi:10.1016/j.jacc.2005.08.045
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(7288):601–605. doi:10.1038/nature08804
Kikuchi K, Gupta V, Wang J, Holdway JE, Wills AA, Fang Y, Poss KD (2011a) tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration. Development 138(14):2895–2902. doi:10.1242/dev.067041
Kikuchi K, Holdway JE, Major RJ, Blum N, Dahn RD, Begemann G, Poss KD (2011b) Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell 20(3):397–404. doi:10.1016/j.devcel.2011.01.010
Kim J, Wu Q, Zhang Y, Wiens KM, Huang Y, Rubin N, Shimada H, Handin RI, Chao MY, Tuan TL, Starnes VA, Lien CL (2010) PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. Proc Natl Acad Sci U S A 107(40):17206–17210. doi:10.1073/pnas.0915016107
Kubin T, Poling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lorchner H, Schimanski S, Szibor M, Warnecke H, Braun T (2011) Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell 9(5):420–432. doi:10.1016/j.stem.2011.08.013
Kusano KF, Pola R, Murayama T, Curry C, Kawamoto A, Iwakura A, Shintani S, Ii M, Asai J, Tkebuchava T, Thorne T, Takenaka H, Aikawa R, Goukassian D, von Samson P, Hamada H, Yoon YS, Silver M, Eaton E, Ma H, Heyd L, Kearney M, Munger W, Porter JA, Kishore R, Losordo DW (2005) Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling. Nat Med 11(11):1197–1204. doi:10.1038/nm1313
Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473(7347):326–335. doi:10.1038/nature10147
Lavine KJ, Ornitz DM (2008) Fibroblast growth factors and Hedgehogs: at the heart of the epicardial signaling center. Trends Genet 24(1):33–40. doi:10.1016/j.tig.2007.10.007
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(3):607–619. doi:10.1016/j.cell.2006.08.052
Li F, Wang X, Capasso JM, Gerdes AM (1996) Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 28(8):1737–1746. doi:10.1006/jmcc.1996.0163
Li P, Cavallero S, Gu Y, Chen TH, Hughes J, Hassan AB, Bruning JC, Pashmforoush M, Sucov HM (2011) IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development. Development 138(9):1795–1805. doi:10.1242/dev.054338
Lien CL, Schebesta M, Makino S, Weber GJ, Keating MT (2006) Gene expression analysis of zebrafish heart regeneration. PLoS Biol 4(8):e260. doi:10.1371/journal.pbio.0040260
Love NR, Chen Y, Ishibashi S, Kritsiligkou P, Lea R, Koh Y, Gallop JL, Dorey K, Amaya E (2013) Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration. Nat Cell Biol 15(2):222–228. doi:10.1038/ncb2659
Malliaras K, Zhang Y, Seinfeld J, Galang G, Tseliou E, Cheng K, Sun B, Aminzadeh M, Marban E (2013) Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med 5(2):191–209. doi:10.1002/emmm.201201737
Mei L, Nave KA (2014) Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron 83(1):27–49. doi:10.1016/j.neuron.2014.06.007
Nemtsas P, Wettwer E, Christ T, Weidinger G, Ravens U (2010) Adult zebrafish heart as a model for human heart? An electrophysiological study. J Mol Cell Cardiol 48(1):161–171. doi:10.1016/j.yjmcc.2009.08.034
Nichols A, Camps M, Gillieron C, Chabert C, Brunet A, Wilsbacher J, Cobb M, Pouyssegur J, Shaw JP, Arkinstall S (2000) Substrate recognition domains within extracellular signal-regulated kinase mediate binding and catalytic activation of mitogen-activated protein kinase phosphatase-3. J Biol Chem 275(32):24613–24621. doi:10.1074/jbc.M001515200
Oberpriller JO, Oberpriller JC (1974) Response of the adult newt ventricle to injury. J Exp Zool 187(2):249–253. doi:10.1002/jez.1401870208
Pachori AS, Custer L, Hansen D, Clapp S, Kemppa E, Klingensmith J (2010) Bone morphogenetic protein 4 mediates myocardial ischemic injury through JNK-dependent signaling pathway. J Mol Cell Cardiol 48(6):1255–1265. doi:10.1016/j.yjmcc.2010.01.010
Piatkowski T, Muhlfeld C, Borchardt T, Braun T (2013) Reconstitution of the myocardium in regenerating newt hearts is preceded by transient deposition of extracellular matrix components. Stem Cells Dev 22(13):1921–1931. doi:10.1089/scd.2012.0575
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(6020):1078–1080. doi:10.1126/science.1200708
Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298(5601):2188–2190. doi:10.1126/science.1077857
Riley PR (2012) An epicardial floor plan for building and rebuilding the mammalian heart. Curr Top Dev Biol 100:233–251. doi:10.1016/B978-0-12-387786-4.00007-5
Rudat C, Kispert A (2012) Wt1 and epicardial fate mapping. Circ Res 111(2):165–169. doi:10.1161/CIRCRESAHA.112.273946
Sallin P, de Preux Charles AS, Duruz V, Pfefferli C, Jazwinska A (2015) A dual epimorphic and compensatory mode of heart regeneration in zebrafish. Dev Biol 399(1):27–40. doi:10.1016/j.ydbio.2014.12.002
Schnabel K, Wu CC, Kurth T, Weidinger G (2011) Regeneration of cryoinjury induced necrotic heart lesions in zebrafish is associated with epicardial activation and cardiomyocyte proliferation. PLoS One 6(4):e18503. doi:10.1371/journal.pone.0018503
Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu TD, Guerquin-Kern JL, Lechene CP, Lee RT (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493(7432):433–436. doi:10.1038/nature11682
Senyo SE, Lee RT, Kuhn B (2014) Cardiac regeneration based on mechanisms of cardiomyocyte proliferation and differentiation. Stem Cell Res 13(3 Pt B):532–541. doi:10.1016/j.scr.2014.09.003
Sleep E, Boue S, Jopling C, Raya M, Raya A, Izpisua Belmonte JC (2010) Transcriptomics approach to investigate zebrafish heart regeneration. J Cardiovasc Med 11(5):369–380. doi:10.2459/JCM.0b013e3283375900
Smart N, Bollini S, Dube KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (2011) De novo cardiomyocytes from within the activated adult heart after injury. Nature 474(7353):640–644. doi:10.1038/nature10188
Szibor M, Poling J, Warnecke H, Kubin T, Braun T (2014) Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration. Cell Mol Life Sci: CMLS 71(10):1907–1916. doi:10.1007/s00018-013-1535-6
van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin SC, Middleton RC, Marban E, Molkentin JD (2014) c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 509(7500):337–341. doi:10.1038/nature13309
Wang J, Martin JF (2014) Macro advances in microRNAs and myocardial regeneration. Curr Opin Cardiol 29(3):207–213. doi:10.1097/HCO.0000000000000050
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(16):3421–3430. doi:10.1242/dev.068601
Wang J, Karra R, Dickson AL, Poss KD (2013) Fibronectin is deposited by injury-activated epicardial cells and is necessary for zebrafish heart regeneration. Dev Biol 382(2):427–435. doi:10.1016/j.ydbio.2013.08.012
Wang J, Cao J, Dickson AL, Poss KD (2015) Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling. Nature. doi:10.1038/nature14325
Washington Smoak I, Byrd NA, Abu-Issa R, Goddeeris MM, Anderson R, Morris J, Yamamura K, Klingensmith J, Meyers EN (2005) Sonic hedgehog is required for cardiac outflow tract and neural crest cell development. Dev Biol 283(2):357–372. doi:10.1016/j.ydbio.2005.04.029
Wills AA, Holdway JE, Major RJ, Poss KD (2008) Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish. Development 135(1):183–192. doi:10.1242/dev.010363
Wu CC, Kruse F, Vasudevarao MD, Junker JP, Zebrowski DC, Fischer K, Noel ES, Grun D, Berezikov E, Engel FB, van Oudenaarden A, Weidinger G, Bakkers J (2016) Spatially resolved genome-wide transcriptional profiling identifies BMP signaling as essential regulator of zebrafish cardiomyocyte regeneration. Dev Cell 36:36–49. doi:10.1016/j.devcel.2015.12.010
Yin VP, Thomson JM, Thummel R, Hyde DR, Hammond SM, Poss KD (2008) Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish. Genes Dev 22(6):728–733. doi:10.1101/gad.1641808
Yin VP, Lepilina A, Smith A, Poss KD (2012) Regulation of zebrafish heart regeneration by miR-133. Dev Biol 365(2):319–327. doi:10.1016/j.ydbio.2012.02.018
Yoshizumi M, Lee WS, Hsieh CM, Tsai JC, Li J, Perrella MA, Patterson C, Endege WO, Schlegel R, Lee ME (1995) Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts. J Clin Invest 95(5):2275–2280. doi:10.1172/JCI117918
Yu F, Li R, Parks E, Takabe W, Hsiai TK (2010) Electrocardiogram signals to assess zebrafish heart regeneration: implication of long QT intervals. Ann Biomed Eng 38(7):2346–2357. doi:10.1007/s10439-010-9993-6
Zebrowski DC, Engel FB (2013) The cardiomyocyte cell cycle in hypertrophy, tissue homeostasis, and regeneration. Rev Physiol Biochem Pharmacol 165:67–96. doi:10.1007/112_2013_12
Zhang R, Han P, Yang H, Ouyang K, Lee D, Lin YF, Ocorr K, Kang G, Chen J, Stainier DY, Yelon D, Chi NC (2013) In vivo cardiac reprogramming contributes to zebrafish heart regeneration. Nature 498(7455):497–501. doi:10.1038/nature12322
Zhao L, Borikova AL, Ben-Yair R, Guner-Ataman B, MacRae CA, Lee RT, Burns CG, Burns CE (2014) Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Proc Natl Acad Sci U S A 111(4):1403–1408. doi:10.1073/pnas.1311705111
Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109–113. doi:10.1038/nature07060
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Wu, CC., Weidinger, G. (2016). Cardiac Regeneration in Zebrafish. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-27583-3_10
Download citation
DOI: https://doi.org/10.1007/978-3-319-27583-3_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-27581-9
Online ISBN: 978-3-319-27583-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)