Jacobs, J Roger (McMaster University)

Purpose

The aim of this proposal is to reveal the mechanisms of cell-to-extracellular matrix (ECM) interaction that regulate development and reshaping of organs like the heart. The ECM is a network of glycoproteins and proteoglycans that are the substrate that bears cell and tissue tension, which also protects tissues and provides a source of molecules that instruct the behavior of cells. Here I propose experiments to test the hypothesis that adhesion signals communicate information that modifies the composition, spatial organisation and physical properties of local ECM. My program employs the fruitfly heart as a genetic model with simple morphology, and focus on the activity of extracellular digestive enzymes (proteases) on cardiac ECM throughout development and aging. Our published works demonstrate that ongoing changes in heart muscle adhesion signaling affect heart form and function. We established that the size and location of the inner vessel wall is regulated by the activity of the two Matrix MetalloProteases (MMPs). This provides the backdrop for our analysis of how changes in ECM composition and organisation remodel tissue form and function. This work supports a deeper understanding of how extracellular mechanisms generate diversity of morphology and respond to external factors during growth and aging.