The role of met receptor in morphogenesis and renewal of the intestinal epithelium

点击翻译按钮获取中文摘要

The functional integrity of the intestinal epithelium in the developing and adult digestive tract relies on a tight control of proliferation, survival, migration, invasion, as well as morphogenesis of various epithelial cell populations. These events are dictated by a concerted interplay between growth factors signals produced by epithelial and surrounding mesenchymal cells. The hepatocyte growth factor (HGF) is a pleiotropic factor of mesenchymal cell origin, which is well known to promote and maintain tissue organization of various vital organs. HGF accomplishes its functions through the specific activation of the Met receptor present at the cell surface of epithelial cells. Biological processes regulated by the Met/HGF receptor axis include epithelial cells proliferation, survival, migration, invasion, as well as morphogenesis. Several lines of evidence suggest that the Met/HGF receptor axis may play key functions in the development and renewal of the intestinal epithelium. However, because of the early embryonic death of HGF or Met receptor-deficient mice, little is known about the specific role of HGF and the Met/HGF receptor in the regulation of these events The overall objective of my research program is to define the function of HGF and the Met receptor in the formation and renewal of the intestinal epithelium. For this we will exploit various cellular and molecular biological approaches applied to various epithelial models to define mechanistically the intracellular signaling pathways downstream of the Met receptor that are implicated in biological processes fundamental to the developmental morphogenesis and the renewal of the intestinal epithelium.