Udo Häcker

Adult barrier epithelia such as the skin or the intestinal epithelium are constantly exposed to environmental toxins and infectious pathogens. The long term maintenance and homeostasis of these tissues therefore requires efficient mechanisms for regeneration and replacement of damaged cells. The regenerative abilities of many tissues have been found to rely on stem cells that can proliferate upon demand and give rise to new differentiating cells in order to maintain homeostasis. This stem cell-based mechanism of tissue renewal must be tightly regulated since loss of homeostasis can result in cell stress, loss of tissue function, premature aging or cancer. In recent years the Drosophila intestinal epithelium has emerged as a powerful model for the investigation of stem cell-based tissue renewal. The discovery of stem cells in the Drosophila midgut epithelium together with the unrivalled molecular genetics tools available in the Drosophila model system has resulted in a flurry of studies elucidating the molecular mechanisms regulating epithelial homeostasis in this tissue. However, many questions remain unanswered. We are using a molecular genetics approach in the Drosophila intestinal epithelium to identify factors regulating cell renewal at the posttranscriptional level and to investigate the mechanisms controlling ER stress and premature aging in renewing tissues. Recent discoveries have shown that stem cell-based mechanisms controlling tissue renewal in the Drosophila midgut are remarkably similar to the mechanisms at work in vertebrate tissues. Results from our studies are therefore likely to have significant impact on the development of new approaches to counter human disorders caused by loss of homeostasis in barrier epithelia.