Document Detail

How insights from cardiovascular developmental biology have impacted the care of infants and children with congenital heart disease.
MedLine Citation:
PMID:  22640994     Owner:  NLM     Status:  MEDLINE    
To illustrate the impact developmental biology and genetics have already had on the clinical management of the million infants born worldwide each year with CHD, we have chosen three stories which have had particular relevance for pediatric cardiologists, cardiothoracic surgeons, cardiac anesthesiologists, and cardiac nurses. First, we show how Margaret Kirby's finding of the unexpected contribution of an ectodermal cell population - the cranial neural crest - to the aortic arch arteries and arterial pole of the embryonic avian heart provided a key impetus to the field of cardiovascular patterning. Recognition that a majority of patients affected by the neurocristopathy DiGeorge syndrome have a chromosome 22q11 deletion, have also spurred tremendous efforts to characterize the molecular mechanisms contributing to this pathology, assigning a major role to the transcription factor Tbx1. Second, synthesizing the work of the last two decades by many laboratories on a wide gamut of metazoans (invertebrates, tunicates, agnathans, teleosts, lungfish, amphibians, and amniotes), we review the >20 major modifications and additions to the ancient circulatory arrangement composed solely of a unicameral (one-chambered), contractile myocardial tube and a short proximal aorta. Two changes will be discussed in detail - the interposition of a second cardiac chamber in the circulation and the septation of the cardiac ventricle. By comparing the developmental genetic data of several model organisms, we can better understand the origin of the various components of the multicameral (multi-chambered) heart seen in humans. Third, Martina Brueckner's discovery that a faulty axonemal dynein was responsible for the phenotype of the iv/iv mouse (the first mammalian model of human heterotaxy) focused attention on the biology of cilia. We discuss how even the care of the complex cardiac and non-cardiac anomalies seen in heterotaxy syndrome, which have long seemed impervious to advancements in surgical and medical intensive care, may yet yield to strategies grounded in a better understanding of the cilium. The fact that all cardiac defects seen in patients with full-blown heterotaxy can also be seen in patients without obvious laterality defects hints at important roles for ciliary function not only in left-right axis specification but also in cardiovascular morphogenesis. These three developmental biology stories illustrate how the remaining unexplained mortality and morbidity of congenital heart disease can be solved.
Alvin J Chin; Jean-Pierre Saint-Jeannet; Cecilia W Lo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-05-26
Journal Detail:
Title:  Mechanisms of development     Volume:  129     ISSN:  1872-6356     ISO Abbreviation:  Mech. Dev.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-31     Completed Date:  2013-03-19     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9101218     Medline TA:  Mech Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  75-97     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, United States.
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MeSH Terms
Biological Evolution
Cilia / pathology,  ultrastructure
Heart / embryology*
Heart Defects, Congenital / pathology*,  therapy*
Heterotaxy Syndrome / embryology,  pathology
Neural Crest / embryology,  pathology
Grant Support

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