Can recent insights into cardiac development improve our understanding of congenitally malformed hearts?
Congenital cardiac malformations account for one-quarter of all human congenital abnormalities. They are caused by environmental and genetic factors. Despite increasing efforts in fundamental research, as yet, the morphogenesis of only a limited number of malformations has been elucidated. Over the last decades, new genetic modifications have made it possible to manipulate the mammalian embryo. Evidence provided using these transgenic techniques has, over the past decade, necessitated re-evaluation of several developmental processes, important in the understanding of normal as opposed to abnormal cardiac development. In this review, we discuss current understanding of the patterning of the initial heart tube, new insights into formation of the atrial and ventricular chambers, and novel information on the origin of the cells that are added to the heart after formation of the initial tube. All of these advances modify our appreciation of malformations involving the venous and arterial poles. As we demonstrate, this new information sheds light not only on normal cardiac development, but also explains the structure of several previously controversial lesions seen in malformed human hearts.
Horsthuis
Thomas
T
Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam, the Netherlands.
Christoffels
Vincent M
VM
Anderson
Robert H
RH
Moorman
Antoon F M
AF
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000235:genetics*; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D038081:Organogenesis