Homeostasis of the esophageal epithelium: A quest for the stem cell

The aim of this thesis is to further unravel the pathways and genes responsible for epithelial homeostasis in the mouse esophagus. Whereas a single layer of columnar epithelium lines most of the gastrointestinal tract, the esophagus is covered with a multilayered squamous epithelium. Proliferative cells reside within the basal layer from which they move upwards and differentiate. Upon reaching the lumen cells are shed off to travel in the direction of the stomach. We still have very limited insight in pathways and genes involved in normal homeostasis of the esophageal epithelium. Enhancing our knowledge of the mechanisms of proliferation and pathways driving differentiation is therefore crucial. It would lead to better understanding of esophageal carcinogenesis, development of Barrett esophagus and tissue repair. The existence of the stem cell in esophagus has thus far been disputed and all cells in the basal layer have been attributed stem cell properties. As this notion contradicts our understanding of the biology of almost all other epithelial tissues, further experimental evidence is needed to clarify the involvement of stem cells in esophageal homeostasis. This effort is especially worth given an implication of stem cells in oncogenic transformation and development of esophageal cancer. To date, a limited number of studies has been performed to address the pathways and genes in control of esophageal epithelial proliferation and differentiation.
In the first part of this thesis the role of Hedgehog signaling in the mouse esophagus and intestine is described. The second part of this thesis revolves around the role of ER stress on the esophageal epithelium.