Fig. 4. Regulation of pancreatic and intestinal cell differentiation by Hes1. (A) In the developing pancreas, the epithelium gives rise to both exocrine and endocrine cells; exocrine cells form acini, whereas endocrine cells emigrate from the epithelium and form islets. The bHLH gene Ptf1a regulates exocrine cell differentiation, whereas Ngn3 promotes the differentiation of all four types of pancreatic endocrine cells [ (glucagon), ß (insulin), (somatostatin) and PP (pancreatic polypeptide) cells]. Hes1 regulates the maintenance of progenitors by inhibiting the expression of Ptf1a and Ngn3. (B) In the adult small intestine, stem cells are found near the bottom of the crypt. The cells moving upwards towards the crypt top and towards the villi differentiate into goblet cells, enteroendocrine cells and enterocytes, whereas those moving downwards towards the crypt bottom differentiate into Paneth cells. Hes1 regulates stem cell maintenance and enterocyte versus non-enterocyte fate choice by repressing Math1, which promotes the development of goblet, enteroendocrine and Paneth cells.