Defining the roles of tissue-specific transcription factors in gut development and disease

Emerging evidence suggests that developmental transcription factors play an essential role in disease such as cancer and inflammation. I will first describe the role of stomach-specific transcription factors in gastric development and cancer. We show that SOX family transcription factors are required for gastric specification and growth, and they become activated during gastric tumorigenesis, playing a key role in cancer initiation. In the second part of my seminar, I will talk about the role of ATOH1, an intestine-specific transcription factor, in stem cell development and inflammation. Atoh1 is essential for secretory lineage differentiation, including Paneth cells. Although we previously demonstrated that Paneth cells are dispensable as an intestinal stem cell niche in the adult, their role during intestinal development is unclear. Our study reveals their essential role in intestinal stem cell development and differentiation to prevent inflammation. These studies demonstrate the critical roles of gut tissue-specific transcription factors in development and disease.