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Heart Embryology: Overview

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Right Heart Pathology

Abstract

Human heart has a complex embryological development process driven by genetic mechanisms that have successive and unitary progression in a global context together with other developments of organogenesis. The first elements of cardiogenesis occur prematurely from mesoderm where cellular differentiation at this level acquires cardiogenic specificity by creating the first heart field. From this stage, cellular multiplication is specific for myocardial, endothelial, and smooth muscle cells through the second heart field. Accordingly to up-to-date evidence, the mechanisms of this process are genetically coordinated mainly by NKX2.5, GATA4, Mef2, TBX5 and Hand which establish not only the structure of the embryonic cord but also the sequential evolution of the differentiation and completion of the cardiac structures including the inlet and outlet paths. First field and second field are the initial particular stages of cardiogenesis. In the primary heart tube, the differentiation into adult anatomical cardiac structures (the atrial and ventricular cavities) begins. The heart tube looping initiates the separation of the primitive atria, ventricle and outflow tract. The separation between these cavities is made by different but concordant mechanisms. Coronarogenesis is the last stage before embryonic heart becomes functional.

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References

  1. Kloesel B, DiNardo JA, Body SC. Cardiac embryology and molecular mechanisms of congenital heart disease: a primer for anesthesiologists. Anesth Analg. 2016;123:551–69. https://doi.org/10.1213/ANE.00000000000014.

  2. Schleich JM, Abdulla T, Summers R, Houyel L. An overview of cardiac morphogenesis. Arch Cardiovasc Dis. 2013;106:612–23. https://doi.org/10.1016/j.acvd.2013.07.001.

    Article  PubMed  Google Scholar 

  3. Epstein JA, Franklin H. Epstein lecture. Cardiac development and implications for heart disease. N Engl J Med. 2010;363:1638–47. https://doi.org/10.1056/NEJMra1003941.

    Article  PubMed  CAS  Google Scholar 

  4. Olson EN, Srivastava D. Molecular pathways controlling heart development. Science. 1996;272:671–6.

    Article  CAS  PubMed  Google Scholar 

  5. Laverriere AC, MacNeill C, Mueller C, Poelmann RE, Burch JB, Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994;269:23177–84.

    PubMed  CAS  Google Scholar 

  6. Olson EN. Gene regulatory networks in the evolution and development of the heart. Science. 2006;313:1922–7. https://doi.org/10.1126/science.1132292.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Kussman BD, Miller-Hance WC. Chapter 4. Development of the cardiovascular system and nomenclature for congenital heart disease. In: Andropoulos DB, Stayer SA, Mossad EB, Miller-Hance WC, editors. Anesthesia for congenital heart disease. 3rd ed. Massachusetts: Wiley-Blackwell; 2015. p. 43.

    Google Scholar 

  8. Hutchins GM, Kessler-Hanna A, Moore GW. Development of the coronary arteries in the embryonic human heart. Circulation. 1988;77:1250–7.

    Article  CAS  PubMed  Google Scholar 

  9. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5:877–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chalajour F, Ma X, Kirk Riemer R. Myocardial self-repair and congenital heart disease, congenital heart disease - selected aspects. In: Syamasundar Rao P, editor. InTech; 2012. doi:https://doi.org/10.5772/26368. https://www.intechopen.com/books/congenital-heart-disease-selected-aspects/myocardial-self-repair-and-congenital-heart-disease.

  11. Gittenberger-de Groot AC, Bartelings MM, Poelmann RE, Haak MC, Jongbloed MR. Embryology of the heart and its impact on understanding fetal and neonatal heart disease. Semin Fetal Neonatal Med. 2013;18:237–44. https://doi.org/10.1016/j.siny.2013.04.008.

    Article  PubMed  Google Scholar 

  12. Martin PS, Kloesel B, Norris RA, Lindsay M, Milan D, Body SC. Embryonic development of the bicuspid aortic valve. J Cardiovasc Dev Dis. 2015;2:248–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lindsey SE, Butcher JT, Yalcin HC. Mechanical regulation of cardiac development. Front Physiol. 2014;5:318. https://doi.org/10.3389/fphys.2014.00318.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ward C, Stadt H, Hutson M, Kirby ML. Ablation of the secondary heart field leads to tetralogy of Fallot and pulmonary atresia. Dev Biol. 2005;284:72–83. https://doi.org/10.1016/j.ydbio.2005.05.003.

    Article  PubMed  CAS  Google Scholar 

  15. Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet. 2005;6:826–35. https://doi.org/10.1038/nrg1710.

    Article  PubMed  CAS  Google Scholar 

  16. Gittenberger-de Groot AC, Bartelings MM, Deruiter MC, Poelmann RE. Basics of cardiac development for the understanding of congenital heart malformations. Pediatr Res. 2005;57:169–76. https://doi.org/10.1203/01.PDR.0000148710.69159.61.

    Article  PubMed  Google Scholar 

  17. Moorman A, Webb S, Brown NA, Lamers W, Anderson RH. Development of the heart: (1) formation of the cardiac chambers and arterial trunks. Heart. 2003;89:806–14.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Harvey RP. Patterning the vertebrate heart. Nat Rev Genet. 2002;3:544–56. https://doi.org/10.1038/nrg843.

    Article  PubMed  CAS  Google Scholar 

  19. Srivastava D. Making or breaking the heart: from lineage determination to morphogenesis. Cell. 2006;126:1037–48. https://doi.org/10.1016/j.cell.2006.09.003.

    Article  PubMed  CAS  Google Scholar 

  20. Vincentz JW, Barnes RM, Firulli AB. Hand factors as regulators of cardiac morphogenesis and implications for congenital heart defects. Birth Defects Res A Clin Mol Teratol. 2011;91:485–94. https://doi.org/10.1002/bdra.20796.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Franco D, Meilhac SM, Christoffels VM, Kispert A, Buckingham M, Kelly RG. Left and right ventricular contributions to the formation of the interventricular septum in the mouse heart. Dev Biol. 2006;294:366–75. https://doi.org/10.1016/j.ydbio.2006.02.045.

    Article  PubMed  CAS  Google Scholar 

  22. Van Mierop LH, Kutsche LM. Development of the ventricular septum of the heart. Heart Vessel. 1985;1:114–9.

    Article  Google Scholar 

  23. Patten BM. The heart. Patten’s foundations of embryology. New York: McGraw-Hill; 1954. p. 545–69.

    Google Scholar 

  24. Anderson RH, Webb S, Brown NA, Lamers W, Moorman A. Development of the heart: (2) septation of the atriums and ventricles. Heart. 2003;89:949–58.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wessels A, Markman MW, Vermeulen JL, Anderson RH, Moorman AF, Lamers WH. The development of the atrioventricular junction in the human heart. Circ Res. 1996;78:110–7.

    Article  CAS  PubMed  Google Scholar 

  26. Van Gils FAW. The development of the human atrioventricular heart valves. J Anat. 1979;128:427.

    Google Scholar 

  27. Lockhart MM, Phelps AL, van den Hoff MJ, Wessels A. The epicardium and the development of the atrioventricular junction in the murine heart. J Dev Biol. 2014;2:1–17. https://doi.org/10.3390/jdb2010001.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Markwald RR, Fitzharris TP, Manasek FJ. Structural development of endocardial cushions. Am J Anat. 1977;148:85–119. https://doi.org/10.1002/aja.1001480108.

    Article  PubMed  CAS  Google Scholar 

  29. Lockhart MM, van den Hoff M, Wessels A. The role of the epicardium in the formation of the cardiac valves in the mouse. In: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H, editors. Etiology and morphogenesis of congenital heart disease from gene function and cellular interaction to morphology. Tokyo: Springer; 2016. p. 161–7. https://doi.org/10.1007/978-4-431-54628-3.

    Chapter  Google Scholar 

  30. Snarr BS, Wirrig EE, Phelps AL, Trusk TC, Wessels A. A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development. Dev Dyn. 2007;236:1287–94. https://doi.org/10.1002/dvdy.21074.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Markwald RR, Norris RA, Moreno-Rodriguez R, Levine RA. Developmental basis of adult cardiovascular diseases: valvular heart diseases. Ann N Y Acad Sci. 2010;1188:177–83. https://doi.org/10.1111/j.1749-6632.2009.05098.x.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lamers WH, Virágh S, Wessels A, Moorman AF, Anderson RH. Formation of the tricuspid valve in the human heart. Circulation. 1995;91:111–21.

    Article  CAS  PubMed  Google Scholar 

  33. de Lange FJ, Moorman AF, Anderson RH, Männer J, Soufan AT, de Gier-de Vries C, Schneider MD, Webb S, van den Hoff MJ, Christoffels VM. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004;95:645–54. https://doi.org/10.1161/01.RES.0000141429.13560.cb.

    Article  PubMed  CAS  Google Scholar 

  34. Restivo A, Piacentini G, Placidi S, Saffirio C, Marino B. Cardiac outflow tract: a review of some embryogenetic aspects of the conotruncal region of the heart. Anat Rec A Discov Mol Cell Evol Biol. 2006;288:936–43. https://doi.org/10.1002/ar.a.20367.

    Article  PubMed  Google Scholar 

  35. Milos NC, Nordstrom DB, Ongaro I, Chow AK. Variations in structure of the outflow tract of the human embryonic heart: a new hypothesis for generating bicuspid aortic semilunar valves. Ann Anat. 2017;211:88–103. https://doi.org/10.1016/j.aanat.2016.12.004.

    Article  PubMed  Google Scholar 

  36. Bajolle F, Zaffran S, Kelly RG, Hadchouel J, Bonnet D, Brown NA, Buckingham ME. Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ Res. 2006;98(3):421–8. https://doi.org/10.1161/01.RES.0000202800.85341.6e.

    Article  PubMed  CAS  Google Scholar 

  37. Neeb Z, Lajiness JD, Bolanis E, Conway SJ. Cardiac outflow tract anomalies. Wiley Interdiscip Dev Biol. 2013;2:499–530. https://doi.org/10.1002/wdev.98.

    Article  CAS  Google Scholar 

  38. Waldo KL, Hutson MR, Ward CC, Zdanowicz M, Stadt HA, Kumiski D, Abu-Issa R, Kirby ML. Secondary heart field contributes myocardium and smooth muscle to the arterial pole of the developing heart. Dev Biol. 2005;281:78 90. https://doi.org/10.1016/j.ydbio.2005.02.012.

    Article  PubMed  CAS  Google Scholar 

  39. Van Mierop LH, Alley RD, Kausel HW, Stranahan A. Pathogenesis of transposition complexes. I. Embryology of the ventricles and great arteries. Am J Cardiol. 1963;12:216–25.

    Article  Google Scholar 

  40. Icardo JM. Development of the outflow tract. A study in hearts with situs solitus and situs inversus. Ann N Y Acad Sci. 1990;588:26–40.

    Article  CAS  PubMed  Google Scholar 

  41. Bartelings MM. The outflow tract of the heart embryologic and morphologic correlations. Ph.D. thesis. The Netherlands: University of Leiden; 1990. doi:10.1046/j.1469-7580.2003.00168.x.

    Google Scholar 

  42. Webb S, Qayyum SR, Anderson RH, Lamers WH, Richardson MK. Septation and separation within the outflow tract of the developing heart. J Anat. 2003;202:327–42.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Wirrig EE, Yutzey KE. Conserved transcriptional regulatory mechanisms in aortic valve development and disease. Arterioscler Thromb Vasc Biol. 2014;34:737–41. https://doi.org/10.1161/ATVBAHA.113.302071.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Wu B, Zhang Z, Lui W, Chen X, Wang Y, Chamberlain AA, Moreno-Rodriguez RA, Markwald RR, O’Rourke BP, Sharp DJ, Zheng D, Lenz J, Baldwin HS, Chang CP, Zhou B. Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling. Cell. 2012;151:1083–96. https://doi.org/10.1016/j.cell.2012.10.023.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Reese DE, Mikawa T, Bader DM. Development of the coronary vessel system. Circ Res. 2002;91:761–8.

    Article  CAS  PubMed  Google Scholar 

  46. Red-Horse K, Ueno H, Weissman IL, Krasnow MA. Coronary arteries form by developmental reprogramming of venous cells. Nature. 2010;464:549–53. https://doi.org/10.1038/nature08873.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Tomanek RJ. Formation of the coronary vasculature during development. Angiogenesis. 2005;8:273–84. https://doi.org/10.1007/s10456-005-9014-9.

    Article  PubMed  Google Scholar 

  48. Tian X, Hu T, Zhang H, He L, Huang X, Liu Q, Yu W, He L, Yang Z, Zhang Z, Zhong TP, Yang X, Yang Z, Yan Y, Baldini A, Sun Y, Lu J, Schwartz RJ, Evans SM, Gittenberger-de Groot AC, Red-Horse K, Zhou B. Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries. Cell Res. 2013;23:1075–90. https://doi.org/10.1038/cr.2013.83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Gourdie RG, Mima T, Thompson RP, Mikawa T. Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system. Development. 1995;121:1423–31.

    PubMed  CAS  Google Scholar 

  50. Wenink AC. Development of the human cardiac conducting system. J Anat. 1976;121(Pt 3):617–31.

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Jongbloed MR, Mahtab EA, Blom NA, Schalij MJ, Gittenberger-de Groot AC. Development of the cardiac conduction system and the possible relation to predilection sites of arrhythmogenesis. Sci World J. 2008;8:239–69. https://doi.org/10.1100/tsw.2008.40.

    Article  CAS  Google Scholar 

  52. Miquerol L, Moreno-Rascon N, Beyer S, Dupays L, Meilhac SM, Buckingham ME, Franco D, Kelly RG. Biphasic development of the mammalian ventricular conduction system. Circ Res. 2010;107:153–61. https://doi.org/10.1161/CIRCRESAHA.110.218156.

    Article  PubMed  CAS  Google Scholar 

  53. Jensen B, Boukens BJ, Postma AV, Gunst QD, van den Hoff MJ, Moorman AF, Wang T, Christoffels VM. Identifying the evolutionary building blocks of the cardiac conduction system. PLoS One. 2012;7:e44231. https://doi.org/10.1371/journal.pone.0044231.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Moorman AF, Christoffels VM. Cardiac chamber formation: development, genes, and evolution. Physiol Rev. 2003;83:1223–67. https://doi.org/10.1152/physrev.00006.2003.

Further Reading

  • O-Rahilly R, Muller F. Developmental stages in human embryos. Washington: Carnegie Institute; 1987.

    Google Scholar 

  • Hutchins GM, Kessler-Hanna A, Moore GW. Development of the coronary arteries in the embryonic human heart. Circulation. 1988;77:1250–7.

    Google Scholar 

  • Oostra RJ, Steding G, Lamers WH, Moorman AFM, Steding S, Viragh S. Scanning electron microscopy atlas of the developing human heart. New York: Springer; 2007.

    Google Scholar 

  • Arráez-Aybar LA, Turrero-Nogués A, Marantos-Gamarra DG. Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection. Cells Tissues Organs. 2008;187:211–20. DOI: https://doi.org/10.1159/000112212.

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Authors and Affiliations

  1. “Titu Maiorescu” University of Medicine, Bucharest, Romania

    Florentina Radu-Ioniţă & Bogdan Cîrciumaru

  2. “Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania

    Florentina Radu-Ioniţă

  3. Department of Cardiology, “Prof. C.C. Iliescu”, Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontaş & Adrian Popa

  4. Department of Cardiovascular Surgery, “Dr. Agripa Ionescu” Military Hospital, Bucharest, Romania

    Viorel Goleanu

  5. Infectious Diseases Department, “Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania

    Bogdan Cîrciumaru

  6. Internal Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

    Daniela Bartoş

  7. Internal Medicine Department, Emergency Hospital Bucharest, Bucharest, Romania

    Daniela Bartoş

  8. Department of Cardiology, “Ovidiu” University Constanta, Emergency County Hospital, Constanta, Romania

    Irinel Parepa

  9. Department of Medicine of Bucharest, “Titu Maiorescu” University, Bucharest, Romania

    Ion C. Ţintoiu

  10. Center for Cardiovascular Diseases, “Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania

    Ion C. Ţintoiu

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  1. Florentina Radu-Ioniţă
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  2. Ecaterina Bontaş
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  3. Viorel Goleanu
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  4. Bogdan Cîrciumaru
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  5. Daniela Bartoş
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  6. Irinel Parepa
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  7. Ion C. Ţintoiu
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  8. Adrian Popa
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Editors and Affiliations

  1. Department of Medicine, Titu Maiorescu University, Bucharest, Romania

    Silviu Ionel Dumitrescu

  2. Department of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

    Ion C. Ţintoiu

  3. Department of Surgery, Chinese University of Hong Kong, Sha Tin, Hong Kong

    Malcolm John Underwood

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Radu-Ioniţă, F. et al. (2018). Heart Embryology: Overview. In: Dumitrescu, S., Ţintoiu, I., Underwood, M. (eds) Right Heart Pathology. Springer, Cham. https://doi.org/10.1007/978-3-319-73764-5_1

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