Biological & Geological Sciences 3053b
Biological & Geological Sciences 3053
(519) 661-2111 x 84704
Extracellular matrix remodelling in Developing Xenopus laevis
Healthy tissue function requires proper cell adhesion, and this adhesion is in part provided by proteins collectively known as the extracellular matrix (ECM). The ECM can be cut and remodelled by proteins called matrix metalloproteinases (MMPs). The function of MMPs is in turn regulated by TIMPs. Many cell types lose their normal functions when cell-ECM interactions are broken, in a process similar to the transformation of healthy cells into uncontrolled cancer cells. We use the frog, Xenopus laevis, as a model system to examine how specific ECM remodelling events control cell fate in specific tissues during development. Several embryological and microinjection techniques are used to investigate MMP and TIMP expression patterns and how they are related to ECM remodelling events, and diverse processes such as cell proliferation, migration and death.
Currently we are focusing on TIMP-3 and a membrane bound MMP named MT3-MMP. TIMPs and MT-MMP are believed to act together to not only regulate ECM remodelling, but also to activate other MMPs. Understanding this regulation would be crucial in our understanding of the roles that these molecules play in development and disease. We are using several expression and inhibition approaches to investigate the roles played by TIMP-3 and MT3 in Xenopus.
We also use the new and powerful technique of frog transgenesis. This involves the addition of a gene of interest into frog sperm and its subsequent incorporation into the genome of the new embryo. These transgenes can be targeted and used to examine the effects of MMP or TIMP overexpression in various developing tissues. Transgenic embryos and cultures of tadpole organs from these transgenic animals can be further manipulated and used to investigate the significance of the transgene in orchestrating ECM remodelling processes and cell differentiation in specific tissues.