© 1995 American Heart Association, Inc.
Articles |
Molecular Regulation of Atrioventricular Valvuloseptal Morphogenesis
From the Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston.
Correspondence to Roger R. Markwald, PhD, Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC 29425.
Key Words: cardiac • valves • endocardium • cushions
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Introduction |
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Malformations of the cardiovascular system are the most frequently occurring type of birth defect, appearing in nearly one percent of newborn infants. The majority of congenital heart defects are due to abnormal development of the valves and membranous septa.1 These tissues arise from mesenchymal outgrowths, referred to as the cardiac cushions, that develop within two regions of the tubular embryonic heart: the atrioventricular (AV) canal and the ventricular outflow tract (conotruncus).2 The formation of the cushions within only these regions of the developing heart may be due to segmental patterning of the primitive heart tube. The cushions initially appear as regionally restricted thickenings of the cardiac jelly, the extracellular matrix (ECM) that resides between the myocardium and endocardium of the primitive heart tube. Cells migrate into the cushions as endothelial cells of the endocardium transform to mesenchyme.2 With regard to the formation of the endocardium, there is evidence for dual cellular origins, both within and outside the heart-forming fields.3 4 5 This may explain, at least in part, the heterogeneity of the endocardium; that is, some cells transform to mesenchyme, whereas other endothelial cells remain vascular.4 6 7 Furthermore, those endocardial and myocardial cells that arise from the heart-forming regions may share a common bipotential precursor. In this paper, we will give an overview of AV valvuloseptal morphogenesis (Fig 1
) from
the commitment of stem cells to this lineage during the onset of
gastrulation, through the establishment of the AV cushions and their
subsequent development into the valves and membranous septa. Moreover,
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