The proposed studies will examine the role of the integrin family of exctrcellular matrix (ECM) receptors in signalling between the ECM and the cell. While these receptors have been known for several years, their precise function(s) have only been theoretical. The proposed studies will address two hypotheses: 1) that the beta1 integrins are important signalling molecules with influence cardiac myofibrillogenesis and the induction of genes which define the hypertrophic myocyte phenotype; and 2) that the cytoplasmic domain of the beta1 provides a means to modulate ventricular chamber formation during cardiac development. To address these hypotheses 3 specific aims will examine: 1) the role of the beta1 cytoplasmic domain in signalling myocytes during cellular organization in the basal state, and during re-organization of the cell during stimulation of the spread/hypertrophic phenotype, in vitro; 2) how beta1 integrin cytoplasmic domain signaling influences normal cardiac development during early Murine cardiogenesis using an ex vivo murine embryo culture system and an ES/embryoid body system; and 3) evaluate the role of the beta1 integrin in cardiac chamber and outflow tract formation in vivo by using cardiac-specific expression of a dominant negative beta1 negative mutant transgenic mice.
Showing the most recent 10 out of 23 publications
