Advertisement

Heart Failure Reviews

, Volume 21, Issue 6, pp 803–813 | Cite as

Zebrafish models of cardiovascular disease

  • Despina Bournele
  • Dimitris Beis
Article

Abstract

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. The most significant risk factors associated with the development of heart diseases include genetic and environmental factors such as hypertension, high blood cholesterol levels, diabetes, smoking, and obesity. Coronary artery disease accounts for the highest percentage of CVD deaths and stroke, cardiomyopathies, congenital heart diseases, heart valve defects and arrhythmias follow. The causes, prevention, and treatment of all forms of cardiovascular disease remain active fields of biomedical research, with hundreds of scientific studies published on a weekly basis. Generating animal models of cardiovascular diseases is the main approach used to understand the mechanism of pathogenesis and also design and test novel therapies. Here, we will focus on recent advances to finding the genetic cause and the molecular mechanisms of CVDs as well as novel drugs to treat them, using a small tropical freshwater fish native to Southeast Asia: the zebrafish (Danio rerio). Zebrafish emerged as a high-throughput but low-cost model organism that combines the advantages of forward and reverse genetics with phenotype-driven drug screenings. Noninvasive imaging allows in vivo analyses of cardiovascular phenotypes. Functional verification of candidate genes from genome-wide association studies has verified the role of several genes in the pathophysiology of CVDs. Also, zebrafish hearts maintain their ability to regenerate throughout their lifetime, providing novel insights to understand human cardiac regeneration.

Keywords

Animal models of cardiovascular disease Zebrafish Regeneration Genetics GWAS studies Basic research 

Notes

Acknowledgments

We thank all the members of the Beis laboratory for comments on the manuscript. Research in the Beis laboratory has been co-financed by the European Union (European Social Fund—ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)—Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Ablain J, Durand E, Yang S, Zhou Y, Zon L (2015) A CRISPR/Cas9 vector system for tissue-specific gene disruption in zebrafish. Dev Cell 32:756–764CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Asakawa K, Kawakami K (2008) Targeted gene expression by the gal4-UAS system in zebrafish. Dev Growth Differ 50:391–399CrossRefPubMedGoogle Scholar
  3. 3.
    Asimaki A, Kapoor S, Plovie E, Arndt K, Adams E, Liu Z, James C, Judge D, Calkins H, Churko J, Wu J, MacRae C, Kléber A, Saffitz J (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci Trans Med 6:240ra74CrossRefGoogle Scholar
  4. 4.
    Baker K, Warren K, Yellen G, Fishman M (1997) Defective “pacemaker” current (Ih) in a zebrafish mutant with a slow heart rate. Proc Natl Acad Sci USA 94:4554–4559CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bamford RN, Roessler E, Burdine RD, Saplakoğlu U, De La Cruz J, Splitt M, Goodship JA, Towbin J, Bowers P, Ferrero GB, Marino B, Schier AF, Shen MM, Muenke M, Casey B (2000) Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects. Nat Genet 26:365–369CrossRefPubMedGoogle Scholar
  6. 6.
    Barbazuk W, Korf I, Kadavi C, Heyen J, Tate S, Wun E, Bedell J, McPherson J, Johnson S (2000) The syntenic relationship of the zebrafish and human genomes. Genome Res 10:1351–1358CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Becker-Heck A, Zohn I, Okabe N, Pollock A, Lenhart K, Sullivan-Brown J, McSheene J, Loges N, Olbrich H, Haeffner K, Fliegauf M, Horvath J, Reinhardt R, Nielsen K, Marthin J, Baktai G, Anderson K, Geisler R, Niswander L, Omran H, Burdine R (2010) The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet 43:79–84CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Becker T, Wullimann M, Becker C, Bernhardt R, Schachner M (1997) Axonal regrowth after spinal cord transection in adult zebrafish. J Comp Neurol 377:577–595CrossRefPubMedGoogle Scholar
  9. 9.
    Beis D, Bartman T, Jin S, Scott I, D’Amico L, Ober E, Verkade H, Frantsve J, Field H, Wehman A, Baier H, Tallafuss A, Bally-Cuif L, Chen J, Stainier D, Jungblut B (2005) Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development (Cambridge, England) 132:4193–4204CrossRefGoogle Scholar
  10. 10.
    Beis D, Stainier D (2006) In vivo cell biology: following the zebrafish trend. Trends Cell Biol 16:105–112CrossRefPubMedGoogle Scholar
  11. 11.
    Bögershausen N, Tsai I, Pohl E, Kiper P, Beleggia F, Percin E, Keupp K, Matchan A, Milz E, Alanay Y, Kayserili H, Liu Y, Banka S, Kranz A, Zenker M, Wieczorek D, Elcioglu N, Prontera P, Lyonnet S, Meitinger T, Stewart A, Donnai D, Strom T, Boduroglu K, Yigit G, Li Y, Katsanis N, Wollnik B (2015) RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome. J Clin Investig 125:3585–3599CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bonetti M, Paardekooper Overman J, Tessadori F, Noël E, Bakkers J, den Hertog J (2014) Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. Development (Cambridge, England) 141:1961–1970CrossRefGoogle Scholar
  13. 13.
    Boselli F, Vermot J (2015) Live imaging and modeling for shear stress quantification in the embryonic zebrafish heart. Methods (San Diego, Calif) 94:129–134CrossRefGoogle Scholar
  14. 14.
    Burns C, Milan D, Grande E, Rottbauer W, MacRae C, Fishman M (2006) High-throughput assay for small molecules that modulate zebrafish embryonic heart rate. Nat Chem Biol 1:263–264CrossRefGoogle Scholar
  15. 15.
    Chablais F, Veit J, Rainer G, Jaźwińska A (2011) The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 11:21CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chen JN, Haffter P, Odenthal J, Vogelsang E, Brand M, van Eeden FJ, Furutani-Seiki M, Granato M, Hammerschmidt M, Heisenberg CP, Jiang YJ, Kane DA, Kelsh RN, Mullins MC, Nüsslein-Volhard C (1996) Mutations affecting the cardiovascular system and other internal organs in zebrafish. Development (Cambridge, England) 123:293–302Google Scholar
  17. 17.
    Chetaille P, Preuss C, Burkhard S, Côté JM, Houde C, Castilloux J, Piché J, Gosset N, Leclerc S, Wünnemann F, Thibeault M, Gagnon C, Galli A, Tuck E, Hickson GR, El Amine N, Boufaied I, Lemyre E, de Santa Barbara P, Faure S, Jonzon A, Cameron M, Dietz HC, Gallo-McFarlane E, Benson DW, Moreau C, Labuda D, FORGE Canada Consortium, Zhan SH, Shen Y, Jomphe M, Jones SJ, Bakkers J, Andelfinger G (2014) Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nat Genet 46:1245–1249CrossRefPubMedGoogle Scholar
  18. 18.
    Chi N, Shaw R, Jungblut B, Huisken J, Ferrer T, Arnaout R, Scott I, Beis D, Xiao T, Baier H, Jan L, Tristani-Firouzi M, Stainier D (2008) Genetic and physiologic dissection of the vertebrate cardiac conduction system. PLoS Biol 6(5):e109CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Choi W, Gemberling M, Wang J, Holdway J, Shen M, Karlstrom R, Poss K (2013) In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development (Cambridge, England) 140:660–666CrossRefGoogle Scholar
  20. 20.
    Curado S, Anderson R, Jungblut B, Mumm J, Schroeter E, Stainier D (2007) Conditional targeted cell ablation in zebrafish: a new tool for regeneration studies. Dev Dyn 236:1025–1035CrossRefPubMedGoogle Scholar
  21. 21.
    Cutler C, Multani P, Robbins D, Kim HT, Le T, Hoggatt J, Pelus LM, Desponts C, Chen YB, Rezner B, Armand P, Koreth J, Glotzbecker B, Ho VT, Alyea E, Isom M, Kao G, Armant M, Silberstein L, Hu P, Soiffer RJ, Scadden DT, Ritz J, Goessling W, North TE, Mendlein J, Ballen K, Zon LI, Antin JH, Shoemaker DD (2013) Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 122:3074–3081CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Davis E, Zhang Q, Liu Q, Diplas B, Davey L, Hartley J, Stoetzel C, Szymanska K, Ramaswami G, Logan C, Muzny D, Young A, Wheeler D, Cruz P, Morgan M, Lewis L, Cherukuri P, Maskeri B, Hansen N, Mullikin J, Blakesley R, Bouffard G, Comparative N, Gyapay G, Rieger S, Tönshoff B, Kern I, Soliman N, Neuhaus T, Swoboda K, Kayserili H, Gallagher T, Lewis R, Bergmann C, Otto E, Saunier S, Scambler P, Beales P, Gleeson J, Maher E, Attié-Bitach T, Dollfus H, Johnson C, Green E, Gibbs R, Hildebrandt F, Pierce E, Katsanis N (2011) TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat Genet 43:189–196CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Davison J, Akitake C, Goll M, Rhee J, Gosse N, Baier H, Halpern M, Leach S, Parsons M (2007) Transactivation from gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafish. Dev Biol 304:811–824CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Di Donato V, De Santis F, Auer T, Testa N, Sánchez-Iranzo H, Mercader N, Concordet JP, Del Bene F (2016) 2C-Cas9: a versatile tool for clonal analysis of gene function. Genome Res 26:681–692CrossRefPubMedGoogle Scholar
  25. 25.
    Dina C, Bouatia-Naji N, Tucker N, Delling FN, Toomer K, Durst R, Perrocheau M, Fernandez-Friera L, Solis J, Le Tourneau T, Chen M-H, Probst V, Bosse Y, Pibarot P, Zelenika D, Lathrop M, Hercberg S, Roussel R, Benjamin EJ, Bonnet F, Lo SH, Dolmatova E, Simonet F, Lecointe S, Kyndt F, Redon R, Le Marec H, Froguel P, Ellinor PT, Vasan RS, Bruneval P, Markwald RR, Norris RA, Milan DJ, Slaugenhaupt SA, Levine RA, Schott J-J, Hagege AA, France MVP, Jeunemaitre X (2015) Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nat Genet 47:1206–1211CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Driever W, Solnica-Krezel L, Schier A, Neuhauss S, Malicki J, Stemple D, Stainier D, Zwartkruis F, Abdelilah S, Rangini Z, Belak J, Boggs C (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development (Cambridge, England) 123:37–46Google Scholar
  27. 27.
    Eisen J, Smith J (2008) Controlling morpholino experiments: don’t stop making antisense. Development (Cambridge, England) 135:1735–1743CrossRefGoogle Scholar
  28. 28.
    Fisher S, Grice E, Vinton R, Bessling S, McCallion A (2006) Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science (New York, NY) 312:276–279CrossRefGoogle Scholar
  29. 29.
    Frangogiannis N (2006) The mechanistic basis of infarct healing. Antioxid Redox Signal 8:1907–1939CrossRefPubMedGoogle Scholar
  30. 30.
    González-Rosa J, Martín V, Peralta M, Torres M, Mercader N (2011) Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish. Development (Cambridge, England) 138:1663–1674CrossRefGoogle Scholar
  31. 31.
    Haack T, Abdelilah-Seyfried S (2016) The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis. Development (Cambridge, England) 143:373–386CrossRefGoogle Scholar
  32. 32.
    Haffter P, Granato M, Brand M, Mullins MC, Hammerschmidt M, Kane DA, Odenthal J, van Eeden FJ, Jiang Y, Heisenberg CP, Kelsh RN, Furutani-Seiki M, Vogelsang E, Beuchle D, Schach U, Fabian C, Nüsslein-Volhard C (1996) The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development (Cambridge, England) 123:1–36Google Scholar
  33. 33.
    Hoffman J, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39:1890–1900CrossRefPubMedGoogle Scholar
  34. 34.
    Hwang W, Fu Y, Reyon D, Maeder M, Tsai S, Sander J, Peterson R, Yeh J, Joung J (2013) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31:227–229CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Hyde AS, Farmer EL, Easley KE, van Lammeren K, Christoffels VM, Barycki JJ, Bakkers J, Simpson MA (2012) UDP-glucose dehydrogenase polymorphisms from patients with congenital heart valve defects disrupt enzyme stability and quaternary assembly. J Biol Chem 287:32708–32716CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Itou J, Oishi I, Kawakami H, Glass T, Richter J, Johnson A, Lund T (2012) Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Development (Cambridge, England) 139:4133–4142CrossRefGoogle Scholar
  37. 37.
    Jin S, Herzog W, Santoro M, Mitchell T, Frantsve J, Jungblut B, Beis D, Scott I, D’Amico L, Ober E, Verkade H, Field H, Chi N, Wehman A, Baier H, Stainier D (2007) A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Dev Biol 307:29–42CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Jopling C, Sleep E, Raya M, Martí M, Belmonte I (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kalogirou S, Malissovas N, Moro E, Argenton F, Stainier D, Beis D (2014) Intracardiac flow dynamics regulate atrioventricular valve morphogenesis. Cardiovasc Res 104:49–60CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kaufman C, White R, Zon L (2009) Chemical genetic screening in the zebrafish embryo. Nat Protoc 4:1422–1432CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, Robinson BV, Minnix SL, Olbrich H, Severin T, Ahrens P, Lange L, Morillas HN, Noone PG, Zariwala MA, Knowles MR (2007) Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation 115:2814–2821CrossRefPubMedGoogle Scholar
  42. 42.
    Kikuchi K, Holdway J, Major R, Blum N, Dahn R, Begemann G, Poss K (2011) Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell 20:397–404CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Kikuchi K, Holdway J, Werdich A, Anderson R, Fang Y, Egnaczyk G, Evans T, Macrae C, Stainier D, Poss K (2010) Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature 464:601–605CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kim J, Wu Q, Zhang Y, Wiens K, Huang Y, Rubin N, Shimada H, Handin R, Chao M, Tuan T, Starnes V, Lien C (2010) PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. Proc Natl Acad Sci USA 107:17206–17210CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kodo K, Nishizawa T, Furutani M, Arai S, Ishihara K, Oda M, Makino S, Fukuda K, Takahashi T, Matsuoka R, Nakanishi T, Yamagishi H (2012) Genetic analysis of essential cardiac transcription factors in 256 patients with non-syndromic congenital heart defects. Circ J 76:1703–1711CrossRefPubMedGoogle Scholar
  46. 46.
    Konantz M, Balci T, Hartwig U, Dellaire G, André M, Berman J, Lengerke C (2012) Zebrafish xenografts as a tool for in vivo studies on human cancer. Ann N Y Acad Sci 1266:124–137CrossRefPubMedGoogle Scholar
  47. 47.
    Kroehne V, Freudenreich D, Hans S, Kaslin J, Brand M (2011) Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors. Development (Cambridge, England) 138:4831–4841CrossRefGoogle Scholar
  48. 48.
    Lam S, Wu Y, Vega V, Miller L, Spitsbergen J, Tong Y, Zhan H, Govindarajan K, Lee S, Mathavan S, Murthy K, Buhler Liu E, Gong Z (2005) Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression. Nat Biotechnol 24:73–75CrossRefPubMedGoogle Scholar
  49. 49.
    Langheinrich U, Vacun G, Wagner T (2003) Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia. Toxicol Appl Pharmacol 193:370–382CrossRefPubMedGoogle Scholar
  50. 50.
    Lepilina A, Coon A, Kikuchi K, Holdway J, Roberts R, Burns C, Poss K (2006) A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 127:607–619CrossRefPubMedGoogle Scholar
  51. 51.
    Lessman C (2011) The developing zebrafish (Danio rerio): a vertebrate model for high-throughput screening of chemical libraries. Birth Defects Res Part C Embryo Today Rev 93:268–280CrossRefGoogle Scholar
  52. 52.
    Loges N, Olbrich H, Becker-Heck A, Häffner K, Heer A, Reinhard C, Schmidts M, Kispert A, Zariwala M, Leigh M, Knowles Zentgraf H, Seithe H, Nürnberg G, Reinhardt R, Omran H (2009) Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Am J Hum Genet 85:883–889CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    MacRae C, Peterson R (2003) Zebrafish-based small molecule discovery. Chem Biol 10:901–908CrossRefPubMedGoogle Scholar
  54. 54.
    Mellman K, Huisken J, Dinsmore C, Hoppe C, Stainier D (2012) Fibrillin-2b regulates endocardial morphogenesis in zebrafish. Dev Biol 372:111–119CrossRefPubMedGoogle Scholar
  55. 55.
    Milan D, Peterson T, Ruskin J, Peterson R, MacRae C (2003) Drugs that induce repolarization abnormalities cause bradycardia in zebrafish. Circulation 107:1355–1358CrossRefPubMedGoogle Scholar
  56. 56.
    Mitchison HM, Schmidts M, Loges NT, Freshour J, Dritsoula A, Hirst RA, O’Callaghan C, Blau H, Al Dabbagh M, Olbrich H, Beales PL, Yagi T, Mussaffi H, Chung EM, Omran H, Mitchell DR (2012) Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet 44:381–389CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Nasevicius A, Ekker S (2000) Effective targeted gene “knockdown” in zebrafish. Nat Genet 26:216–220CrossRefPubMedGoogle Scholar
  58. 58.
    Noël E, Momenah T, Al-Dagriri K, Al-Suwaid A, Al-Shahrani S, Jiang H, Willekers S, Oostveen Y, Chocron S, Postma A, Bhuiyan Z, Bakkers J (2015) A Zebrafish loss-of-function model for human CFAP53 mutations reveals its specific role in Laterality organ function. Hum Mutat 37:194–200CrossRefPubMedGoogle Scholar
  59. 59.
    North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang IH, Grosser T, Fitzgerald GA, Daley GQ, Orkin SH, Zon LI (2007) Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447:1007–1011CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Orr N, Arnaout R, Gula L, Spears D, Leong-Sit P, Li Q, Tarhuni W, Reischauer S, Chauhan V, Borkovich M, Uppal S, Adler A, Coughlin S, Stainier D, Gollob M (2016) A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation. Nat Commun 7:11303CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Paige S, Thomas S, Stoick-Cooper C, Wang H, Maves L, Sandstrom R, Pabon L, Reinecke H, Pratt G, Keller G, Moon R, Stamatoyannopoulos J, Murry C (2012) A temporal chromatin signature in human embryonic stem cells identifies regulators of cardiac development. Cell 151:221–232CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Papakyriakou A, Kefalos P, Sarantis P, Tsiamantas C, Xanthopoulos K, Vourloumis D, Beis D (2014) A zebrafish in vivo phenotypic assay to identify 3-aminothiophene-2-carboxylic acid-based angiogenesis inhibitors. Assay Drug Dev Technol 12:527–535CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Pelster B, Burggren W (1996) Disruption of hemoglobin oxygen transport does not impact oxygen-dependent physiological processes in developing embryos of zebra fish (Danio rerio). Circ Res 79:358–362CrossRefPubMedGoogle Scholar
  64. 64.
    Peterson R, Link B, Dowling J, Schreiber S (2000) Small molecule developmental screens reveal the logic and timing of vertebrate development. Proc Natl Acad Sci USA 97:12965–12969CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Peterson R, Macrae C (2011) Systematic approaches to toxicology in the zebrafish. Annu Rev Pharmacol Toxicol 52:433–453CrossRefPubMedGoogle Scholar
  66. 66.
    Peterson R, Shaw S, Peterson T, Milan D, Zhong T, Schreiber S, MacRae C, Fishman M (2004) Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Nat Biotechnol 22:595–599CrossRefPubMedGoogle Scholar
  67. 67.
    Porrello E, Mahmoud A, Simpson E, Hill J, Richardson J, Olson E, Sadek H (2011) Transient regenerative potential of the neonatal mouse heart. Science (New York, NY) 331:1078–1080CrossRefGoogle Scholar
  68. 68.
    Poss K, Keating M, Nechiporuk A (2003) Tales of regeneration in zebrafish. Dev Dyn 226:202–210CrossRefPubMedGoogle Scholar
  69. 69.
    Poss K, Wilson L, Keating M (2002) Heart regeneration in zebrafish. Science (New York, NY) 298:2188–2190CrossRefGoogle Scholar
  70. 70.
    Postlethwait J, Yan Y, Gates M, Horne S, Amores A, Brownlie A, Donovan A, Egan E, Force A, Gong Z, Goutel C, Fritz A, Kelsh R, Knapik E, Liao E, Paw B, Ransom D, Singer A, Thomson M, Abduljabbar T, Yelick P, Beier D, Joly J, Larhammar D, Rosa F, Westerfield M, Zon L, Johnson S, Talbot W (1998) Vertebrate genome evolution and the zebrafish gene map. Nat Genet 18:345–349CrossRefPubMedGoogle Scholar
  71. 71.
    Ramspacher C, Steed E, Boselli F, Ferreira R, Faggianelli N, Roth S, Spiegelhalter C, Messaddeq N, Trinh L, Liebling M, Chacko N, Tessadori F, Bakkers J, Laporte J, Hnia K, Vermot J (2015) Developmental alterations in heart Biomechanics and skeletal muscle function in desmin mutants suggest an early pathological root for desminopathies. Cell reports 11:1564–1576CrossRefPubMedGoogle Scholar
  72. 72.
    Renz M, Otten C, Faurobert E, Rudolph F, Zhu Y, Boulday G, Duchene J, Mickoleit M, Dietrich A, Ramspacher C, Steed E, Manet-Dupé S, Benz A, Hassel D, Vermot J, Huisken J, Tournier-Lasserve E, Felbor U, Sure U, Albiges-Rizo C, Abdelilah-Seyfried S (2015) Regulation of β1 integrin-klf2-mediated angiogenesis by CCM proteins. Dev Cell 32:181–190CrossRefPubMedGoogle Scholar
  73. 73.
    Rossi A, Kontarakis Z, Gerri C, Nolte H, Hölper S, Krüger M, Stainier D (2015) Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524:230–233CrossRefPubMedGoogle Scholar
  74. 74.
    Santoro M (2014) Antiangiogenic cancer drug using the zebrafish model. Arterioscler Thromb Vasc Biol 34:1846–1853CrossRefPubMedGoogle Scholar
  75. 75.
    Schnabel K, Wu C, 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:e18503CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Schulte E, Kousi M, Tan P, Tilch E, Knauf F, Lichtner P, Trenkwalder C, Högl B, Frauscher B, Berger K, Fietze I, Hornyak M, Oertel W, Bachmann C, Zimprich A, Peters A, Gieger C, Meitinger T, Müller-Myhsok B, Katsanis N, Winkelmann J (2014) Targeted resequencing and systematic in vivo functional testing identifies rare variants in MEIS1 as significant contributors to restless legs syndrome. Am J Hum Genet 95:85–95CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Schulte-Merker S, Stainier D (2014) Out with the old, in with the new: reassessing morpholino knockdowns in light of genome editing technology. Development (Cambridge, England) 141:3103–3104CrossRefGoogle Scholar
  78. 78.
    Sehnert A, Huq A, Weinstein B, Walker C, Fishman M, Stainier D (2002) Cardiac troponin T is essential in sarcomere assembly and cardiac contractility. Nat Genet 31:106–110CrossRefPubMedGoogle Scholar
  79. 79.
    Smith KA, Joziasse IC, Chocron S, van Dinther M, Guryev V, Verhoeven MC, Rehmann H, der van Smagt JJ, Doevendans PA, Cuppen E, Mulder BJ, Ten Dijke P, Bakkers J (2009) Dominant-negative ALK2 allele associates with congenital heart defects. Circulation 119:3062–3069CrossRefPubMedGoogle Scholar
  80. 80.
    Stainier D, Fouquet B, Chen J, Warren K, Weinstein B, Meiler S, Mohideen M, Neuhauss S, Solnica-Krezel L, Schier A, Zwartkruis F, Stemple D, Malicki J, Driever W, Fishman M (1996) Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. Development (Cambridge, England) 123:285–292Google Scholar
  81. 81.
    Steed E, Boselli F, Vermot J (2015) Hemodynamics driven cardiac valve morphogenesis. Biochim Biophys Acta 1863(7 Pt B):1760–1766. doi: 10.1016/j.bbamcr.2015.11.014 PubMedGoogle Scholar
  82. 82.
    Szeto D, Griffin K, Kimelman D (2002) HrT is required for cardiovascular development in zebrafish. Development (Cambridge, England) 129:5093–5101Google Scholar
  83. 83.
    Tran T, Sneed B, Haider J, Blavo D, White A, Aiyejorun T, Baranowski T, Rubinstein A, Doan T, Dingledine R, Sandberg E (2007) Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Cancer Res 67:11386–11392CrossRefPubMedGoogle Scholar
  84. 84.
    Vihtelic TS, Hyde DR (2000) Light-induced rod and cone cell death and regeneration in the adult albino zebrafish (Danio rerio) retina. J Neurobiol 44:289–307CrossRefPubMedGoogle Scholar
  85. 85.
    Wang J, Cao J, Dickson A, Poss K (2015) Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling. Nature 522:226–230CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Wang J, Panáková D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, Singh SP, Dickson AL, Lin Y-F, Sabeh KM, Werdich AA, Yelon D, MacRae CA, Poss KD (2011) The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development 138:3421–3430CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Wang X, Yu Q, Wu Q, Bu Y, Chang N, Yan S, Zhou X, Zhu X, Xiong J (2013) Genetic interaction between pku300 and fbn2b controls endocardial cell proliferation and valve development in zebrafish. J Cell Sci 126:1381–1391CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    White R, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, Bourque C, Dovey M, Goessling W, Burns C, Zon L (2008) Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2:183–189CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Wu CC, Kruse F, Vasudevarao MD, Junker JP, Zebrowski DC, Fischer K, Noël ES, Grün 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 36:36–49CrossRefPubMedGoogle Scholar
  90. 90.
    Zaghloul N, Katsanis N (2011) Zebrafish assays of ciliopathies. Methods Cell Biol 105:257–272CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Zareba W, Cygankiewicz I (2008) Long QT syndrome and short QT syndrome. Prog Cardiovasc Dis 51:264–278CrossRefPubMedGoogle Scholar
  92. 92.
    Zebrowski D, Becker R, Engel F (2016) Towards regenerating the mammalian heart: challenges in evaluating experimentally induced adult mammalian cardiomyocyte proliferation. Am J Physiol Heart Circ Physiol 310(9):H1045–H1054CrossRefPubMedGoogle Scholar
  93. 93.
    Zebrowski D, Vergarajauregui S, Wu C, Piatkowski T, Becker R, Leone M, Hirth S, Ricciardi F, Falk N, Giessl A, Just S, Braun T, Weidinger G, Engel F (2015) Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes. Elife. doi: 10.7554/eLife.05563 PubMedPubMedCentralGoogle Scholar
  94. 94.
    Zhao L, Borikova A, Ben-Yair R, Guner-Ataman B, MacRae C, Lee R, Burns C (2014) Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Proc Natl Acad Sci USA 111:1403–1408CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Zebrafish Disease Models Lab, Center for Clinical Experimental Surgery and Translational ResearchBiomedical Research Foundation Academy of AthensAthensGreece
  2. 2.Faculty of MedicineNational and Kapodistrian University of AthensAthensGreece

Personalised recommendations