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The quintessence of the making of the heart

Published online by Cambridge University Press:  18 April 2005

Adriana C. Gittenberger-de Groot
Affiliation:
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

Abstract

In my Mannheimer lecture, designed to meet the needs of a mainly clinical audience, I present aspects of cardiac development that link basic science to clinically relevant problems. During development of the cardiac tube, and its subsequent changes as a dextrally looped structure, which is still connected to the dorsal body wall by a venous and an arterial pole, there are basic requirements. These consist of the development of myocardium, endocardium and the interposed cardiac jelly from the cardiogenic plates. In this primitive heart tube, septation and valvar formation then take place to convert it into a four-chambered heart. I demonstrate that the refining of the above events cannot take place without the addition of extracardiac populations of cells. These are presented as the “quintessence of heart development”, and consist of cells derived from the neural crest, along with epicardially derived cells. Without these contributions, the embryos uniformly die of cardiac insufficiency. Important contributions are made by the cells derived from the neural crest to septation and the formation of the arterial valves, and possibly in differentiation of the central conduction system. The epicardially derived cells are essential for formation of the interstitial fibroblasts and the myocardium, as well as the coronary vascular system. I conclude by discussing specific malformations of the heart that might be linked to these extracardiac contributions.

Type
Mannheimer Lecture
Copyright
© 2003 Cambridge University Press

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Footnotes

The article is the text of the Mannheimer lecture, given on the occasion of the 37th Meeting of the Association of European Pediatric Cardiology, Porto, Portugal, 2002.

References

Drake CJ, Hungerford JE, Little CD. Morphogenesis of the first blood vessels. Ann NY Acad Sci 1998; 857: 155179.Google Scholar
Blom NA, Gittenberger-de Groot AC, DeRuiter MC, Poelmann RE, Mentink MM, Ottenkamp J. Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity. Circulation 1999; 99: 800806.Google Scholar
Gittenberger-de Groot AC, DeRuiter MC, Bartelings MM, Poelmann RE. Embryology of congenital heart disease. In: Crawford MH, DiMarco JP, (eds). Cardiology, First. Mosby International Limited, London, 2001; pp 2.12.10.
Christoffels VM, Habets PEMH, Franco D, et al. Chamber formation and morphogenesis in the developing mammalian heart. Dev Biol 2000; 223: 266278.Google Scholar
Franco D, Kelly R, Lamers WH, Buckingham M, Moorman AFM. Regionalized transcriptional domains of myosin light chain 3f transgenes in the embryonic mouse heart: morphogenetic implications. Dev Biol 1997; 188: 1733.Google Scholar
Kirby ML, Gale TF, Stewart DE. Neural crest cells contribute to normal aorticopulmonary septation. Science 1983; 220: 10591061.Google Scholar
Bergwerff M, Verberne ME, DeRuiter MC, Poelmann RE, Gittenberger-de Groot AC. Neural crest cell contribution to the developing circulatory system. Implications for vascular morphology? Circ Res 1998; 82: 221231.Google Scholar
Epstein JA, Li J, Lang D, et al. Migration of cardiac neural crest cells in Splotch embryos. Development 2000; 127: 18691878.Google Scholar
Waldo KL, Lo CW, Kirby ML. Connexin 43 expression reflects neural crest patterns during cardiovascular development. Dev Biol 1999; 208: 307323.Google Scholar
Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM. Fate of the mammalian cardiac neural crest. Development 2000; 127: 16071616.Google Scholar
Poelmann RE, Gittenberger-de Groot AC. A subpopulation of apoptosis-prone cardiac neural crest cells targets to the venous pole: multiple functions in heart development? Dev Biol 1999; 207: 271286.Google Scholar
Poelmann RE, Mikawa T, Gittenberger-de Groot AC. Neural crest cells in outflow tract septation of the embryonic chicken heart: differentiation and apoptosis. Dev Dyn 1998; 212: 373384.Google Scholar
van Mierop LHS, Kutsche LM. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am J Cardiol 1986; 58: 133137.Google Scholar
Lindsay EA, Vitelli F, Su H, et al. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 2001; 410: 97101.Google Scholar
Blom NR, Gittenberger-de Groot AC, DeRuiter MC, Poelmann RE, Mentink MMT, Ottenkamp J. Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression. Circulation 1999; 99: 800806.Google Scholar
Rentschler S, Vaidya DM, Tamaddon H, et al. Visualization and functional characterization of the developing murine cardiac conduction system. Development 2001; 128: 17851792.Google Scholar
Vrancken Peeters M-PFM, Mentink MMT, Poelmann RE, Gittenberger-de Groot AC. Cytokeratins as a marker for epicardial formation in the quail embryo. Anat Embryol (Berl) 1995; 191: 503508.Google Scholar
Virágh Sz, Gittenberger-de Groot AC, Poelmann RE, Kálmán F. Early development of quail heart epicardium and associated vascular and glandular structures. Anat Embryol 1993; 188: 381393.Google Scholar
Gittenberger-de Groot AC, Vrancken Peeters M-PFM, Mentink MMT, Gourdie RG, Poelmann RE. Epicardial derived cells, EPDCs, contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 1998; 82: 10431052.Google Scholar
Vrancken Peeters M-PFM, Gittenberger-de Groot AC, Mentink MMT, Poelmann RE. Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial–mesenchymal transformation of the epicardium. Anat Embryol 1999; 199: 367378.Google Scholar
Poelmann RE, Gittenberger-de Groot AC, Mentink MMT, Bökenkamp R, Hogers B. Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras. Circ Res 1993; 73: 559568.Google Scholar
Gittenberger-de Groot AC, Vrancken Peeters M-PFM, Bergwerff M, Mentink MMT, Poelmann RE. Epicardial outgrowth inhibition leads to compensatory mesothelial outflow tract collar and abnormal cardiac septation and coronary formation. Circ Res 2000; 87: 969971.Google Scholar
Gittenberger-de Groot AC, Sauer U, Bindl L, Babic R, Essed CE, Buhlmeyer K. Competition of coronary arteries and ventriculo-coronary arterial communications in pulmonary atresia with intact ventricular septum. Int J Cardiol 1988; 18: 243258.Google Scholar
Chaoui R, Tennstedt C, Göldner B, Bollmann R. Prenatal diagnosis of ventriculo-coronary communications in a second-trimester fetus using transvaginal and transabdominal color Doppler sonography. Ultrasound Obstet Gynecol 1997; 9: 194197.Google Scholar
Gittenberger-de Groot AC, Tennstedt C, Chaoui R, Lie-Venema H, Sauer U, Poelmann RE. Ventriculo coronary arterial communications (VCAC) and myocardial sinusoids in hearts with pulmonary artresia with intact ventricular septum: two different diseases. Prog Pediatr Cardiol 2001; 13: 157164.Google Scholar