Crucial Role of PDX-1 in Pancreas Development, β-Cell Differentiation, and Induction of Surrogate β-Cells

Hideaki Kaneto; Takeshi Miyatsuka; Toshihiko Shiraiwa; Kaoru Yamamoto; Ken Kato; Yoshio Fujitani; Taka-aki Matsuoka

Abstract

Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, β-cell differentiation, and maintaining mature β-cell function. At an early stage of embryonic development, PDX-1 is initially expressed in the gut region when the foregut endoderm becomes committed to common pancreatic precursor cells. During pancreas development, PDX-1 expression is maintained in precursor cells, and later it becomes restricted to β-cells. In mature β-cells, PDX-1 transactivates the insulin gene and other genes involved in glucose sensing and metabolism, such as GLUT2 and glucokinase. MafA is a recently isolated β-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulinproducing cell production. Furthermore, these transcription factors play a crucial role in inducing surrogate β-cells from non-β- cells and thus could be therapeutic targets for diabetes.

Keywords: PDX-1, MafA, transcription factor, pancreas development, β-cell differentiation, surrogate β-cells

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