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Experimental Biology and Medicine 232:866-880 (2007)
© 2007 Society for Experimental Biology and Medicine

MINIREVIEW

Signal Transduction in Early Heart Development (II): Ventricular Chamber Specification, Trabeculation, and Heart Valve Formation

Michael Wagner1 and M. A. Q. Siddiqui1

Center for Cardiovascular and Muscle Research and the Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203

To whom requests for reprints should be addressed at 1 Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203. E-mail: michael.wagner{at}downstate.edu or maq.siddiqui{at}downstate.edu

The formation of a four-chambered heart with ventricular chambers aligned in a left-right orientation begins with the rightward looping of the linear heart tube in accordance with the left-right embryonic axis. The functional specification of the ventricular chambers in the looped heart occurs with the formation of a trabeculated myocardium along the outer curvature of the realigned heart tube. Two major signal transduction pathways are involved in this process, the retinoic acid and neuregulin signaling pathways, with the retinoic acid pathway also participating in rightward heart tube looping. With the establishment of the atrial and ventricular chambers, maintenance of a unidirectional flow of blood between the two chambers must be ensured. To achieve this, heart valves develop at the atrioventricular juncture. This process begins with formation of endocardial cushions, the primordia of heart valves, and ends with formation of heart valve leaflets. Underlying this process is a complex network of signal transduction pathways that mediate communication between the endocardial and myocardial cell layers to form the endocardial cushions and nascent heart valve. Some of the signaling molecules involved are vascular endothelial growth factor, Wnts, bone morphogenetic proteins, epidermal growth factor, hyaluronic acid, neurofibromin, and calcium.

Key Words: ventricular specification • trabeculation • endocardial cushions • retinoic acid • neuregulins • vascular endothelial growth factor • Notch






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