This is especially significant as ECMs are, by their insoluble nature, very refractile to biochemical analysis. The analysis of the HA synthase type II-null mice shows that indeed HA is required for certain ECM swellings in the embryo as predicted. That this involves a failure in HA signaling is reinforced by finding that the defect may be overridden by expression of an activated form of the Ras GTP-binding protein in the endothelial cells in an organ culture model of cell migration. A genetic approach has been used to show that structural molecules of the ECM also have the capacity to convey 'information', possibly through a cell surface receptor in this case. Certain complex morphogenetic processes such as epithelial invasion of the ECM can be studied in vitro using an organ culture model.
Cardiac development is rather morphologically complex.
Diagrams will be provided with the paper to help interpret the basics. The genetic analysis of signaling via Ras and other GTP-binding proteins has been greatly facilitated by the discovery of mutant forms of these proteins that are either constitutively active or constitutively inactive. These forms are dominant in the presence of normal cellular Ras and thus can be used simply by transfecting normal cells. Questions for Discussion 1. HA appears early in development, but morphological differences are not observed until E8.5 in the Has2-null embryos.