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Zebrafish models of cardiovascular disease

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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.

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References

  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 32:756–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Asakawa K, Kawakami K (2008) Targeted gene expression by the gal4-UAS system in zebrafish. Dev Growth Differ 50:391–399

    Article  CAS  PubMed  Google Scholar 

  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 6:240ra74

    Article  Google Scholar 

  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 94:4554–4559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 26:365–369

    Article  CAS  PubMed  Google Scholar 

  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 10:1351–1358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 43:79–84

    Article  PubMed  PubMed Central  Google Scholar 

  8. Becker T, Wullimann M, Becker C, Bernhardt R, Schachner M (1997) Axonal regrowth after spinal cord transection in adult zebrafish. J Comp Neurol 377:577–595

    Article  CAS  PubMed  Google Scholar 

  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) 132:4193–4204

    Article  CAS  Google Scholar 

  10. Beis D, Stainier D (2006) In vivo cell biology: following the zebrafish trend. Trends Cell Biol 16:105–112

    Article  CAS  PubMed  Google Scholar 

  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 125:3585–3599

    Article  PubMed  PubMed Central  Google Scholar 

  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) 141:1961–1970

    Article  CAS  Google Scholar 

  13. Boselli F, Vermot J (2015) Live imaging and modeling for shear stress quantification in the embryonic zebrafish heart. Methods (San Diego, Calif) 94:129–134

    Article  Google Scholar 

  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 1:263–264

    Article  Google Scholar 

  15. Chablais F, Veit J, Rainer G, Jaźwińska A (2011) The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 11:21

    Article  PubMed  PubMed Central  Google Scholar 

  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) 123:293–302

    CAS  Google Scholar 

  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 46:1245–1249

    Article  CAS  PubMed  Google Scholar 

  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):e109

    Article  PubMed  PubMed Central  Google Scholar 

  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) 140:660–666

    Article  CAS  Google Scholar 

  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 236:1025–1035

    Article  CAS  PubMed  Google Scholar 

  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 122:3074–3081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 43:189–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 304:811–824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 26:681–692

    Article  PubMed  Google Scholar 

  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 47:1206–1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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) 123:37–46

    CAS  Google Scholar 

  27. Eisen J, Smith J (2008) Controlling morpholino experiments: don’t stop making antisense. Development (Cambridge, England) 135:1735–1743

    Article  CAS  Google Scholar 

  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) 312:276–279

    Article  CAS  Google Scholar 

  29. Frangogiannis N (2006) The mechanistic basis of infarct healing. Antioxid Redox Signal 8:1907–1939

    Article  CAS  PubMed  Google Scholar 

  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) 138:1663–1674

    Article  Google Scholar 

  31. Haack T, Abdelilah-Seyfried S (2016) The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis. Development (Cambridge, England) 143:373–386

    Article  CAS  Google Scholar 

  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) 123:1–36

    CAS  Google Scholar 

  33. Hoffman J, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39:1890–1900

    Article  PubMed  Google Scholar 

  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 31:227–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 287:32708–32716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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) 139:4133–4142

    Article  CAS  Google Scholar 

  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 307:29–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jopling C, Sleep E, Raya M, Martí M, Belmonte I (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kalogirou S, Malissovas N, Moro E, Argenton F, Stainier D, Beis D (2014) Intracardiac flow dynamics regulate atrioventricular valve morphogenesis. Cardiovasc Res 104:49–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kaufman C, White R, Zon L (2009) Chemical genetic screening in the zebrafish embryo. Nat Protoc 4:1422–1432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 115:2814–2821

    Article  PubMed  Google Scholar 

  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 20:397–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 464:601–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 107:17206–17210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 76:1703–1711

    Article  CAS  PubMed  Google Scholar 

  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 1266:124–137

    Article  PubMed  Google Scholar 

  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) 138:4831–4841

    Article  CAS  Google Scholar 

  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 24:73–75

    Article  PubMed  Google Scholar 

  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 193:370–382

    Article  CAS  PubMed  Google Scholar 

  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 127:607–619

    Article  CAS  PubMed  Google Scholar 

  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 93:268–280

    Article  CAS  Google Scholar 

  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 85:883–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. MacRae C, Peterson R (2003) Zebrafish-based small molecule discovery. Chem Biol 10:901–908

    Article  CAS  PubMed  Google Scholar 

  54. Mellman K, Huisken J, Dinsmore C, Hoppe C, Stainier D (2012) Fibrillin-2b regulates endocardial morphogenesis in zebrafish. Dev Biol 372:111–119

    Article  CAS  PubMed  Google Scholar 

  55. Milan D, Peterson T, Ruskin J, Peterson R, MacRae C (2003) Drugs that induce repolarization abnormalities cause bradycardia in zebrafish. Circulation 107:1355–1358

    Article  PubMed  Google Scholar 

  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 44:381–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Nasevicius A, Ekker S (2000) Effective targeted gene “knockdown” in zebrafish. Nat Genet 26:216–220

    Article  CAS  PubMed  Google Scholar 

  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 37:194–200

    Article  PubMed  Google Scholar 

  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 447:1007–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 7:11303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 151:221–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 12:527–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 79:358–362

    Article  CAS  PubMed  Google Scholar 

  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 97:12965–12969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Peterson R, Macrae C (2011) Systematic approaches to toxicology in the zebrafish. Annu Rev Pharmacol Toxicol 52:433–453

    Article  PubMed  Google Scholar 

  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 22:595–599

    Article  CAS  PubMed  Google Scholar 

  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) 331:1078–1080

    Article  CAS  Google Scholar 

  68. Poss K, Keating M, Nechiporuk A (2003) Tales of regeneration in zebrafish. Dev Dyn 226:202–210

    Article  PubMed  Google Scholar 

  69. Poss K, Wilson L, Keating M (2002) Heart regeneration in zebrafish. Science (New York, NY) 298:2188–2190

    Article  CAS  Google Scholar 

  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 18:345–349

    Article  CAS  PubMed  Google Scholar 

  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 11:1564–1576

    Article  CAS  PubMed  Google Scholar 

  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 32:181–190

    Article  CAS  PubMed  Google Scholar 

  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 524:230–233

    Article  CAS  PubMed  Google Scholar 

  74. Santoro M (2014) Antiangiogenic cancer drug using the zebrafish model. Arterioscler Thromb Vasc Biol 34:1846–1853

    Article  CAS  PubMed  Google Scholar 

  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:e18503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 95:85–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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) 141:3103–3104

    Article  CAS  Google Scholar 

  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 31:106–110

    Article  CAS  PubMed  Google Scholar 

  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 119:3062–3069

    Article  CAS  PubMed  Google Scholar 

  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) 123:285–292

    CAS  Google Scholar 

  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

    PubMed  Google Scholar 

  82. Szeto D, Griffin K, Kimelman D (2002) HrT is required for cardiovascular development in zebrafish. Development (Cambridge, England) 129:5093–5101

    CAS  Google Scholar 

  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 67:11386–11392

    Article  CAS  PubMed  Google Scholar 

  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 44:289–307

    Article  CAS  PubMed  Google Scholar 

  85. Wang J, Cao J, Dickson A, Poss K (2015) Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling. Nature 522:226–230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 138:3421–3430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 126:1381–1391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2:183–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 36:36–49

    Article  CAS  PubMed  Google Scholar 

  90. Zaghloul N, Katsanis N (2011) Zebrafish assays of ciliopathies. Methods Cell Biol 105:257–272

    Article  PubMed  PubMed Central  Google Scholar 

  91. Zareba W, Cygankiewicz I (2008) Long QT syndrome and short QT syndrome. Prog Cardiovasc Dis 51:264–278

    Article  PubMed  Google Scholar 

  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–H1054

    Article  PubMed  Google Scholar 

  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

    PubMed  PubMed Central  Google Scholar 

  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 111:1403–1408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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.

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Authors and Affiliations

  1. Zebrafish Disease Models Lab, Center for Clinical Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece

    Despina Bournele & Dimitris Beis

  2. Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Despina Bournele

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  1. Despina Bournele
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  2. Dimitris Beis
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Correspondence to Dimitris Beis.

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Bournele, D., Beis, D. Zebrafish models of cardiovascular disease. Heart Fail Rev 21, 803–813 (2016). https://doi.org/10.1007/s10741-016-9579-y

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