
The heart is the first organ to form during embryonic development. The formation of the heart is a very complex and highly regulated process. Failure of the heart to properly form stops further development or results in congenital heart defects. Congenital heart defects are the most prevalent type of birth defects observed in infants. Congenital heart defects occur at a rate of 1-2% of all births with heart valve defects being the second most common type of heart defect. These types of heart defects are a major contributor to infant mortality. Infants with such defects require surgery within the first year of life often followed by subsequent interventions. The emotional, physical and monetary stress for these families is overwhelming. Profound understandings into the causes of congenital heart defects have only begun to develop over the last decade. We use animal els to study normal and abnormal cardiovascular development with an emphasis on heart valve and septal formation. We have generated and use transgenic and knockout mouse lines that have hyper- and hypoplastic embryonic valve tissue. These els allow us to pursue functional studies and define regulatory cascades involved in cardiovascular development. We show that the extracellular matrix component, hyaluronan, influences ErbB receptor tyrosine kinase signaling as required for normal heart valve development. Our continued studies are revealing novel molecules involved in heart development and are also allowing us to gain a more comprehensive understanding of cardiovascular development. Medicine and basic research have reached a point whereby understanding the normal development of the functioning heart and the consequences of pathologic conditions will lead to novel remedies for congenital heart defects as well as valvular disease in adults.
Klewer SE, Yatskievych T, Pogreba K, Stevens MV, Antin PB, Camenisch TD. Feb 2006. Has2 expression in heart forming regions is independent of BMP signaling. Gene Expr Patterns,2006 Feb 1;
Rodgers LS Lalani S Hardy KM Xiang X Broka D Antin PB Camenisch TD. Sep 2006. Depolymerized hyaluronan induces vascular endothelial growth factor, a negative regulator of developmental epithelial-to-mesenchymal transformation. Circ Res, 99:583-9
Stevens MV Parker P Vaillancourt RR Camenisch TD. Oct 2006. MEKK4 regulates developmental EMT in the embryonic heart. Dev Dyn, 235:2761-70
Lopez JI, Camenisch TD, Stevens MV, Sands BJ, McDonald J, Schroeder JA. Aug 2005. CD44 attenuates metastatic invasion during breast cancer progression. Cancer Res, 65:6755-63