Regulation and consequences of extracellular matrix remodelling protease activity in the developing zebrafish embryo.

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Living cells secrete a number of proteins which make up a mechanically tough and biochemcially complex extracellular matrix (ECM). This matrix is what gives most tissues their mechanical properties and many of their biological functions. In order for tissues to grow, heal, or otherwise change shape, cells must degrade the ECM using enzymes called Matrix Metalloproteinases (MMPs). The objectives of this research proposal are to investigate how MMP activity is regulated during the embryonic development of the zebrafish embryo, and to better understand the biologically relevant consequences of that activity. The zebrafish embryo is useful in this study, because, unlike the embryos of mice or other mammals, the fish embryo develops externally, rapidly and it is transparent, allowing us to more easily observe the effects of our experiments. We have developed novel techniques that allow us to see the distribution and activation patterns of the MMPs, and also to determine what molecules they are acting on in the live embryo. Not only will this research help us better understand how ECM remodeling is regulated during embryonic development, it should also provide some insight into how to treat pathologies arising from the mis-regulation of MMP activity, such as arthritis, heart disease, stroke, and cancer.