Role of Fibroblast-Growth Factor Signalling in Epithelial Remodelling

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Our body is composed of different organs and tissues, which all work together to deliver the functions that identify us as healthy human beings. The major types of tissues in our body are sheet-like assemblies of cells, called epithelia. Epithelia have a top and a bottom side. The top or apical side faces the outside world (skin) or the lumen of an organ (gut, glands, kidney) and the bottom or basal side faces the inside of the organism. This polarized architecture is essential for the function of epithelia. For example a disruption of the gut epithelium will impair uptake of nutrients and eventually cause inflammation. Loss of epithelial polarity can also cause diseases such as fibrosis, where excessive connective tissue is formed. Moreover, loss of epithelial polarity is a key event in the dissemination of cancer cells into different parts of the body, a process called metastasis. The mechanisms that cancer cells utilize to become malignant are often recapitulations of events that normally occur during embryogenesis. During development a primitive embryonic epithelium is formed that partially undergoes a conversion to non-epithelial (mesenchymal) cells. These mesenchymal cells develop further into muscles, heart and blood cells. Improper cell movements during these stages of development can result in abortive development and congenital defects in animals and humans.Our research project addresses the question how cell signalling can elicit the transition of an epithelial cell to a mesenchymal cell (called EMT). Our laboratory will utilize genetics to identify molecules important for epithelial cells to loose their epithelial polarity in EMT. Research on human embryos is highly problematic for obvious ethical reasons. Modern biomedical research uses model organisms to study basic biological mechanisms because these are often very similar in different organisms. For example the principle genes that control cell division are quite similar from yeast to man. We utilize the fruit fly as a model system to find genes that are involved in EMT. The principal molecules that control the development of the fly are also critical for the development of human embryos. This finding was awarded the Nobel Prize for Medicine in 1995. Furthermore, more than 75% of all genes that have been identified to cause diseases in humans are also present in the fly. Therefore the fly is an excellent system to perform detailed research which findings can eventually be translated from the basic research laboratory to the clinic.