Heart valve development: endothelial cell signaling and differentiation.
During 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.
Armstrong
Ehrin J
EJ
Vascular Biology Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, MA 02115, USA.
Bischoff
Joyce
J
D000818:Animals; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D006351:Heart Valves / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D006801:Humans; D051379:Mice; D008955:Models, Cardiovascular; D011506:Proteins / Q000502:physiology; D015398:Signal Transduction
D011506:Proteins