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Heart valve development: endothelial cell signaling and differentiation Armstrong EJ; Bischoff JCirc Res 2004[Sep]; 95 (5): 459-70During the past decade, single gene disruption in mice and large-scale mutagenesis screens in zebrafish have elucidated many fundamental genetic pathways that govern early heart patterning and differentiation. Specifically, a number of genes have been revealed serendipitously to play important and selective roles in cardiac valve development. These initially surprising results have now converged on a finite number of signaling pathways that regulate endothelial proliferation and differentiation in developing and postnatal heart valves. This review highlights the roles of the most well-established ligands and signaling pathways, including VEGF, NFATc1, Notch, Wnt/beta-catenin, BMP/TGF-beta, ErbB, and NF1/Ras. Based on the interactions among and relative timing of these pathways, a signaling network model for heart valve development is proposed.|*Models, Cardiovascular[MESH]|*Signal Transduction[MESH]|Animals[MESH]|Cell Differentiation[MESH]|Endothelial Cells/cytology/metabolism[MESH]|Endothelium, Vascular/cytology/*embryology/growth & development/metabolism[MESH]|Heart Valves/cytology/*embryology/growth & development[MESH]|Humans[MESH]|Mice[MESH]|Proteins/physiology[MESH] |