Neurogenin 3 is a Key Transcription Factor for Differentiation of the Endocrine Pancreas

摘要

The pancreas is composed of exocrine and endocrine compartments. The endocrine compartment consists of the islets of Langerhans, which contain clusters comprising four types of cells: glucagon-producing α cells, somatostatin-producing δ cells, pancreatic polypeptide-producing PP cells, and insulin-producing β cells. Because an inadequate mass of functioning pancreatic β cells is a feature of both type 1 and type 2 diabetes, β cell replacement therapy is considered to be a potential curative treatment. If we can understand how β cells develop normally, it may become possible to use that knowledge to reprogram various cell types to differentiate into new β cells. Thus, studies of pancreatic development may contribute to overcoming diabetes. One of the main roles of β cells is secretion of insulin in response to an increase of the blood glucose level. To accomplish this, pancreatic β cells express numerous genes that are essential for glucose-responsive insulin secretion, such as glucokinase, Kir6.2, and SUR1, as well as insulin. To allow the expression of such strictly selected multiple sets of genes, various differentiation steps are required during pancreatic development. As is the case for other types of cells, recent studies have identified several transcription factors that control the activation and repression of a large number of genes during pancreatic development and cell biology studies have revealed how these factors function. Accumulation of such knowledge has revealed that transcription factors orchestrate the intricate pathways of cellular growth, death, and differentiation by direct regulation of gene expression. Amongst the transcription factors in this well-organized cascade, neurogenin 3 (Ngn3) plays a key role in determining the fate of cells in the endocrine pancreas. This article discusses the role of Ngn3 during pancreatic development, the regulation of Ngn3 expression and how Ngn3 activates the expression of downstream genes.