Intestinal Specific Gene Regulation by Transcription Factors Gata4 and Hnfla in Vivo

textabstractThe mammalian small intestine is responsible for the terminal digestion and absorption of nutrients, water homeostasis, and the elimination of waste products, which in turn, are essential processes for life. These processes however, are easily disrupted by infection, inflammatory processes such as Crohn’s disease, cancer, and resection. The small intestine is equipped with specific proteins, such as enzymes to digest nutrients (digestion) and ‘transporters’ to carry the nutrients into the body (absorption). These tools for digestion and absorption are specifically expressed in the enterocytes of the small intestine and this expression is regulated by a complex of regulatory proteins among which intestinal transcription factors. These regulatory proteins are proposed to be important for intestinal gene expression, differentiation and development and are central to intestinal function. A better insight into the role that specific transcription factors play in these processes will thus complement our understanding of the regulation of intestinal function. Such fundamental knowledge will provide critical insight into disease processes and repair mechanisms of the intestinal epithelium, and identify potential avenues of intervention to correct lost or deficient intestinal function. The research described in this thesis investigates the role of the transcription factors Gata4 and Hnf1< in intestinal gene expression in vivo