Skip to main content
SpringerLink
Log in

Cardiac Development

  • Chapter
Handbook of Cardiac Anatomy, Physiology, and Devices

  • 130k Accesses

Abstract

The first heart field (FHF), second heart field (SHF), cardiac neural crest (CNC), and proepicardial organ (PEO) are the four major embryonic regions involved in vertebrate heart development. They each make an important contribution to overall cardiac development with complex developmental timing and regulation. This chapter describes how these regions interact to form the final structure of the heart in relationship to the developmental timeline of human embryology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Schoenwolf GC, Bleyl BB, Brauer PR, Francis-West PH (eds) (2009) Larsen’s human embryology, 4th edn. Churchill Livingstone Elsevier, Philadelphia

    Google Scholar 

  2. Martinsen BJ (2005) Reference guide to the stages of chick heart embryology. Dev Dyn 233:1217–1237

    Article  PubMed  Google Scholar 

  3. Srivastava D, Olson EN (2000) A genetic blueprint for cardiac development. Nature 407:221–226

    Article  CAS  PubMed  Google Scholar 

  4. Jensen B, Wang T, Christoffels VM, Moorman AFM (2013) Evolution and development of the building plan of the vertebrate heart. Biochim Biophys Acta 1833:783–794

    Article  CAS  PubMed  Google Scholar 

  5. Sperling SR (2011) Systems biology approaches to heart development and congenital heart disease. Cardiovasc Res 91:269–278

    Article  CAS  PubMed  Google Scholar 

  6. Fahed AC, Gelb BD, Seidman JG, Seidman CE (2013) Genetics of congenital heart disease: the glass half empty. Circ Res 112:707–720

    Article  CAS  PubMed  Google Scholar 

  7. Kelly RG, Brown NA, Buckingham ME (2001) The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm. Dev Cell 1:435–440

    Article  CAS  PubMed  Google Scholar 

  8. Mjaatvedt CH, Nakaoka T, Moreno-Rodriguez R et al (2001) The outflow tract of the heart is recruited from a novel heart-forming field. Dev Biol 238:97–109

    Article  CAS  PubMed  Google Scholar 

  9. Waldo KL, Kumiski DH, Wallis KT et al (2001) Conotruncal myocardium arises from a secondary heart field. Development 128:3179–3188

    CAS  PubMed  Google Scholar 

  10. Xin M, Olson EN, Bassel-Duby R (2013) Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair. Nat Rev Mol Cell Biol 14:529–541

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kodo K, Yamagishi H (2011) A decade of advances in the molecular embryology and genetics underlying congenital heart defects. Circ J 75:2296–2304

    Article  CAS  PubMed  Google Scholar 

  12. Kelly RG (2012) The second heart field. Curr Top Dev Biol 100:33–65

    Article  CAS  PubMed  Google Scholar 

  13. Van den Berg G, Abu-Issa R, de Boer BA et al (2009) A caudal proliferating growth center contributes to both poles of the forming heart tube. Circ Res 104:179–188

    Article  PubMed Central  PubMed  Google Scholar 

  14. De Boer BA, van den Berg G, de Boer PAJ et al (2012) Growth of the developing mouse heart: an interactive qualitative and quantitative 3D atlas. Dev Biol 368:203–213

    Article  PubMed  Google Scholar 

  15. Brade T, Pane LS, Moretti A et al (2013) Embryonic heart progenitors and cardiogenesis. Cold Spring Harb Perspect Med 3:a013847

    Article  PubMed Central  PubMed  Google Scholar 

  16. Lin CJ, Lin CY, Chen CH et al (2012) Partitioning the heart: mechanisms of cardiac septation and valve development. Development 139:3277–3299

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Francou A, Saint-Michel E, Mesbah K et al (2013) Second heart field cardiac progenitor cells in the early mouse embryo. Biochim Biophys Acta 1833:795–798

    Article  CAS  PubMed  Google Scholar 

  18. Kelly RG, Buckingham ME (2002) The anterior heart-forming field: voyage to the arterial pole of the heart. Trends Genet 18:210–216

    Article  CAS  PubMed  Google Scholar 

  19. Degenhardt K, Singh MK, Epstein JA (2013) New approaches under development: cardiovascular embryology applied to heart disease. J Clin Invest 123:71–74

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Keyte A, Hutson MR (2012) The neural crest in cardiac congenital anomalies. Differentiation 84:25–40

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Pérez-Pomares JM, de la Pompa JL (2011) Signaling during epicardium and coronary vessel development. Circ Res 109:1429–1442

    Article  PubMed  Google Scholar 

  22. Smart N, Riley PR (2012) The epicardium as a candidate for heart regeneration. Future Cardiol 8:53–69

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Hatada Y, Stern CD (1994) A fate map of the epiblast of the early chick embryo. Development 120:2879–2889

    CAS  PubMed  Google Scholar 

  24. Yutzey KE, Kirby ML (2002) Wherefore heart thou? Embryonic origins of cardiogenic mesoderm. Dev Dyn 223:307–320

    Article  PubMed  Google Scholar 

  25. Garcia-Martinez V, Schoenwolf GC (1993) Primitive-streak origin of the cardiovascular system in avian embryos. Dev Biol 159:706–719

    Article  CAS  PubMed  Google Scholar 

  26. Psychoyos D, Stern CD (1996) Fates and migratory routes of primitive streak cells in the chick embryo. Development 122:1523–1534

    CAS  PubMed  Google Scholar 

  27. DeHaan RL (1963) Organization of the cardiogenic plate in the early chick embryo. Acta Embryol Moprhol Exp 6:26–38

    Google Scholar 

  28. Ehrman LA, Yutzey KE (1999) Lack of regulation in the heart forming region of avian embryos. Dev Biol 207:163–175

    Article  CAS  PubMed  Google Scholar 

  29. Harvey RP, Rosenthal N (eds) (1999) Heart development, 1st edn. Academic, San Diego

    Google Scholar 

  30. Kirby ML (2002) Molecular embryogenesis of the heart. Pediatr Dev Pathol 23:537–544

    Google Scholar 

  31. Nandadasa S, Foulcer S, Apte SS (2014) The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis. Matrix Biol 35:34–41

    Article  CAS  PubMed  Google Scholar 

  32. Lohr JL, Yost HJ (2000) Vertebrate model systems in the study of early heart development: Xenopus and zebrafish. Am J Med Genet 97:248–257

    Article  CAS  PubMed  Google Scholar 

  33. De la Cruz MV, Sánchez Gómez C, Arteaga MM, Argüello C (1977) Experimental study of the development of the truncus and the conus in the chick embryo. J Anat 123:661–686

    PubMed Central  PubMed  Google Scholar 

  34. Dyer LA, Kirby ML (2009) The role of secondary heart field in cardiac development. Dev Biol 336:137–144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Kelly RG (2005) Molecular inroads into the anterior heart field. Trends Cardiovasc Med 15:51–56

    Article  CAS  PubMed  Google Scholar 

  36. Gittenberger-de Groot AC, Vrancken Peeters MP, Bergwerff M et al (2000) Epicardial outgrowth inhibition leads to compensatory mesothelial outflow tract collar and abnormal cardiac septation and coronary formation. Circ Res 87:969–971

    Article  CAS  PubMed  Google Scholar 

  37. Lie-Venema H, van den Akker NMS, Bax NAM et al (2007) Origin, fate, and function of epicardium-derived cells (EPDCs) in normal and abnormal cardiac development. Scientific World Journal 7:1777–1798

    Article  CAS  PubMed  Google Scholar 

  38. Kirby ML, Gale TF, Stewart DE (1983) Neural crest cells contribute to normal aorticopulmonary septation. Science 220:1059–1061

    Article  CAS  PubMed  Google Scholar 

  39. Kirby ML, Stewart DE (1983) Neural crest origin of cardiac ganglion cells in the chick embryo: identification and extirpation. Dev Biol 97:433–443

    Article  CAS  PubMed  Google Scholar 

  40. Kirby ML, Turnage KL, Hays BM (1985) Characterization of conotruncal malformations following ablation of “cardiac” neural crest. Anat Rec 213:87–93

    Article  CAS  PubMed  Google Scholar 

  41. O’Rahilly R, Müller F (2007) The development of the neural crest in the human. J Anat 211:335–351

    Article  PubMed Central  PubMed  Google Scholar 

  42. Porras D, Brown CB (2008) Temporal-spatial ablation of neural crest in the mouse results in cardiovascular defects. Dev Dyn 237:153–162

    Article  CAS  PubMed  Google Scholar 

  43. Hildreth V, Webb S, Bradshaw L et al (2008) Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart. J Anat 212:1–11

    PubMed Central  PubMed  Google Scholar 

  44. Poelmann RE, Jongbloed MRM, Molin DGM et al (2004) The neural crest is contiguous with the cardiac conduction system in the mouse embryo: a role in induction? Anat Embryol (Berl) 208:389–393

    Article  CAS  Google Scholar 

  45. Poelmann RE, Gittenberger-de Groot AC (1999) A subpopulation of apoptosis-prone cardiac neural crest cells targets to the venous pole: multiple functions in heart development? Dev Biol 207:271–286

    Article  CAS  PubMed  Google Scholar 

  46. Bockman DE, Redmond ME, Kirby ML (1989) Alteration of early vascular development after ablation of cranial neural crest. Anat Rec 225:209–217

    Article  CAS  PubMed  Google Scholar 

  47. Waldo K, Miyagawa-Tomita S, Kumiski D, Kirby ML (1998) Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: aortic sac to ventricular septal closure. Dev Biol 196:129–144

    Article  CAS  PubMed  Google Scholar 

  48. Waldo KL, Lo CW, Kirby ML (1999) Connexin 43 expression reflects neural crest patterns during cardiovascular development. Dev Biol 208:307–323

    Article  CAS  PubMed  Google Scholar 

  49. Martinsen BJ, Groebner NJ, Frasier AJ, Lohr JL (2003) Expression of cardiac neural crest and heart genes isolated by modified differential display. Gene Expr Patterns 3:407–411

    Article  CAS  PubMed  Google Scholar 

  50. Martinsen BJ, Frasier AJ, Baker CVH, Lohr JL (2004) Cardiac neural crest ablation alters Id2 gene expression in the developing heart. Dev Biol 272:176–190

    Article  CAS  PubMed  Google Scholar 

  51. Anderson RH, Webb S, Brown NA et al (2003) Development of the heart: (2) Septation of the atriums and ventricles. Heart 89:949–958

    Article  PubMed Central  PubMed  Google Scholar 

  52. Lamers WH, Moorman AFM (2002) Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis. Circ Res 91:93–103

    Article  CAS  PubMed  Google Scholar 

  53. Komiyama M, Ito K, Shimada Y (1987) Origin and development of the epicardium in the mouse embryo. Anat Embryol (Berl) 176:183–189

    Article  CAS  Google Scholar 

  54. Noden DM, Poelmann RE, Gittenberger-de Groot AC (1995) Cell origins and tissue boundaries during outflow tract development. Trends Cardiovasc Med 5:69–75

    Article  CAS  PubMed  Google Scholar 

  55. Mikawa T, Gourdie RG (1996) Pericardial mesoderm generates a population of coronary smooth muscle cells migrating into the heart along with ingrowth of the epicardial organ. Dev Biol 174:221–232

    Article  CAS  PubMed  Google Scholar 

  56. Noden DM (1990) Origins and assembly of avian embryonic blood vessels. Ann N Y Acad Sci 588:236–249

    Article  CAS  PubMed  Google Scholar 

  57. Hood LC, Rosenquist TH (1992) Coronary artery development in the chick: origin and deployment of smooth muscle cells, and the effects of neural crest ablation. Anat Rec 234:291–300

    Article  CAS  PubMed  Google Scholar 

  58. Bu L, Jiang X, Martin-Puig S et al (2009) Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature 460:113–117

    Article  CAS  PubMed  Google Scholar 

  59. Laugwitz K-L, Moretti A, Lam J et al (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653

    Article  CAS  PubMed  Google Scholar 

  60. Musunuru K, Domian IJ, Chien KR (2010) Stem cell models of cardiac development and disease. Annu Rev Cell Dev Biol 26:667–687

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Anderson PAW (2000) Developmental cardiac physiology and myocardial function. In: Moller JH, Hoffman JIE (eds) Pediatric cardiovascular medicine. Churchill Livingstone, New York, pp 35–57

    Google Scholar 

  62. Huttenbach Y, Ostrowski ML, Thaller D, Kim HS (2001) Cell proliferation in the growing human heart: MIB-1 immunostaining in preterm and term infants at autopsy. Cardiovasc Pathol 10:119–123

    Article  CAS  PubMed  Google Scholar 

  63. Kern FH, Bengur AR, Bello EA (1996) Developmental cardiac physiology. In: Pediatric intensive care, 3rd edn. Lippincott, Williams and Wilkins, Baltimore, pp 397–423

    Google Scholar 

  64. Kim HD, Kim DJ, Lee IJ et al (1992) Human fetal heart development after mid-term: morphometry and ultrastructural study. J Mol Cell Cardiol 24:949–965

    Article  CAS  PubMed  Google Scholar 

  65. Beltrami AP, Urbanek K, Kajstura J et al (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 344:1750–1757

    Article  CAS  PubMed  Google Scholar 

  66. Anversa P, Leri A (2013) Innate regeneration in the aging heart: healing from within. Mayo Clin Proc 88:871–883

    Article  PubMed Central  PubMed  Google Scholar 

  67. Rota M, Leri A, Anversa P (2014) Human heart failure: is cell therapy a valid option? Biochem Pharmacol 88:129–138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Vick GW, Fisher DA (1998) Cardiac metabolism. In: Garson A (ed) The science and practice of pediatric cardiology. Williams and Wilkens, Baltimore, pp 155–169

    Google Scholar 

  69. Opie LH (1991) Carbohydrates and lipids. In: Opie LH (ed) The heart: physiology and metabolism, 2nd edn. Raven, New York, pp 208–246

    Google Scholar 

  70. Price KM, Littler WA, Cummins P (1980) Human atrial and ventricular myosin light-chains subunits in the adult and during development. Biochem J 191:571–580

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Morano M, Zacharzowski U, Maier M et al (1996) Regulation of human heart contractility by essential myosin light chain isoforms. J Clin Invest 98:467–473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Morano I (1999) Tuning the human heart molecular motors by myosin light chains. J Mol Med (Berl) 77:544–555

    Article  CAS  Google Scholar 

  73. Boheler KR, Carrier L, de la Bastie D et al (1991) Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts. J Clin Invest 88:323–330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Anderson PAW, Kleinman CS, Lister G, Talner N (1998) Cardiovascular function during normal fetal and neonatal development and with hypoxic stress. In: Polin RA, Fox WW (eds) Fetal and neonatal physiology, 2nd edn. Saunders, Philadelphia, pp 837–890

    Google Scholar 

  75. Hewett TE, Grupp IL, Grupp G, Robbins J (1994) Alpha-skeletal actin is associated with increased contractility in the mouse heart. Circ Res 74:740–746

    Article  CAS  PubMed  Google Scholar 

  76. Muthuchamy M, Grupp IL, Grupp G et al (1995) Molecular and physiological effects of overexpressing striated muscle beta-tropomyosin in the adult murine heart. J Biol Chem 270:30593–30603

    Article  CAS  PubMed  Google Scholar 

  77. Palmiter KA, Kitada Y, Muthuchamy M et al (1996) Exchange of beta- for alpha-tropomyosin in hearts of transgenic mice induces changes in thin filament response to Ca2+, strong cross-bridge binding, and protein phosphorylation. J Biol Chem 271:11611–11614

    Article  CAS  PubMed  Google Scholar 

  78. Muthuchamy M, Boivin GP, Grupp IL, Wieczorek DF (1998) Beta-tropomyosin overexpression induces severe cardiac abnormalities. J Mol Cell Cardiol 30:1545–1557

    Article  CAS  PubMed  Google Scholar 

  79. Kim SH, Kim HS, Lee MM (2002) Re-expression of fetal troponin isoforms in the postinfarction failing heart of the rat. Circ J 66:959–964

    Article  CAS  PubMed  Google Scholar 

  80. Hunkeler NM, Kullman J, Murphy AM (1991) Troponin I isoform expression in human heart. Circ Res 69:1409–1414

    Article  CAS  PubMed  Google Scholar 

  81. Purcell IF, Bing W, Marston SB (1999) Functional analysis of human cardiac troponin by the in vitro motility assay: comparison of adult, foetal and failing hearts. Cardiovasc Res 43:884–891

    Article  CAS  PubMed  Google Scholar 

  82. Morimoto S, Goto T (2000) Role of troponin I isoform switching in determining the pH sensitivity of Ca(2+) regulation in developing rabbit cardiac muscle. Biochem Biophys Res Commun 267:912–917

    Article  CAS  PubMed  Google Scholar 

  83. Tanaka H, Sekine T, Nishimaru K, Shigenobu K (1998) Role of sarcoplasmic reticulum in myocardial contraction of neonatal and adult mice. Comp Biochem Physiol A Mol Integr Physiol 120:431–438

    Article  CAS  PubMed  Google Scholar 

  84. Buchhorn R, Hulpke-Wette M, Ruschewski W et al (2002) Beta-receptor downregulation in congenital heart disease: a risk factor for complications after surgical repair? Ann Thorac Surg 73:610–613

    Article  PubMed  Google Scholar 

  85. Schiffmann H, Flesch M, Häuseler C et al (2002) Effects of different inotropic interventions on myocardial function in the developing rabbit heart. Basic Res Cardiol 97:76–87

    Article  CAS  PubMed  Google Scholar 

  86. Sun LS (1999) Regulation of myocardial beta-adrenergic receptor function in adult and neonatal rabbits. Biol Neonate 76:181–192

    Article  CAS  PubMed  Google Scholar 

  87. Dees E, Baldwin HS (2002) New frontiers in molecular pediatric cardiology. Curr Opin Pediatr 14:627–633

    Article  PubMed  Google Scholar 

  88. McFadden DG, Olson EN (2002) Heart development: learning from mistakes. Curr Opin Genet Dev 12:328–335

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Cardiology, Department of Pediatrics, University of Minnesota School of Medicine, East Building, MB 560, 2450 Riverside Avenue, Minneapolis, MN, 55454, USA

    Brad J. Martinsen PhD & Jamie L. Lohr MD

Authors
  1. Brad J. Martinsen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jamie L. Lohr MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brad J. Martinsen PhD .

Editor information

Editors and Affiliations

  1. B172 Mayo, MMC 195, University of Minnesota Department of Surgery, Minneapolis, Minnesota, USA

    Paul A. Iaizzo

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Martinsen, B.J., Lohr, J.L. (2015). Cardiac Development. In: Iaizzo, P. (eds) Handbook of Cardiac Anatomy, Physiology, and Devices. Springer, Cham. https://doi.org/10.1007/978-3-319-19464-6_3

Download citation

Publish with us

Policies and ethics

Search

Navigation