Type VI collagen in the cardiac valves and connective tissue septa during heart development.

A variety of extracellular matrix (ECM) proteins have been shown to be present in the embryonic heart during the morphogenesis of the valves and membranous septa. It is not known if any specific ECM protein is required for the normal morphogenesis of these tissues, but this is of great interest since there is a high incidence of congenital malformations which affect valvular and septal tissues. Interestingly, the alpha 1 and alpha 2 genes of type VI collagen are located within the region of human chromosome 21 thought to be involved in the congenital heart defect phenotype associated with trisomy 21 (Down's syndrome). In this study we examined the distribution and investigated the function of type VI collagen in the cardiac valves and septa of chicken and mouse embryos during various stages of development. Immunohistochemical and in situ hybridization studies revealed a pattern of cardiac expression of type VI collagen which is present from the earliest stages of valve and septum development through the neonatal period. Results from an in vitro bioassay suggest that type VI collagen may play a role in the formation and migration of specific cells in the forming valves and septa. These data support molecular genetic studies which have indicated that type VI collagen is involved in the heart defect phenotype seen in trisomy 21.