How insights from cardiovascular developmental biology have impacted the care of infants and children with congenital heart disease

Alvin J. Chin, Jean-Pierre Saint-Jeannet, Cecilia W. Lo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)75-97
Number of pages23
JournalMechanisms of Development
Volume129
Issue number5-8
DOIs
StatePublished - Jul 2012

Fingerprint

Infant Care
Developmental Biology
Child Care
Heart Diseases
Cilia
Axonemal Dyneins
Heterotaxy Syndrome
DiGeorge Syndrome
Urochordata
Chromosome Deletion
Neural Crest
Amphibians
Invertebrates
Critical Care
Thoracic Aorta
Morphogenesis
Heart Ventricles
Aorta
Transcription Factors
Arteries

Keywords

  • Cilium
  • Congenital heart disease
  • DiGeorge syndrome
  • Heterotaxy syndrome
  • Neural crest
  • Right ventricle

ASJC Scopus subject areas

  • Developmental Biology
  • Embryology

Cite this

How insights from cardiovascular developmental biology have impacted the care of infants and children with congenital heart disease. / Chin, Alvin J.; Saint-Jeannet, Jean-Pierre; Lo, Cecilia W.

In: Mechanisms of Development, Vol. 129, No. 5-8, 07.2012, p. 75-97.

Research output: Contribution to journalArticle

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