[Transcription Factor PAX4: Role in Differentiation of Insulin- Producing β Cells during Pancreas Development and...

PAX4 (Paired Box 4) is a transcription factor that is expressed mainly in the pancreas and plays a key role in the development of insulin-producing β cells at the embryonic stage. In mature cells, PAX4 acts as a main regulator of their adaptation under pathological conditions. The importance of PAX4 to the proper function of pancreatic islets has been demonstrated in studies of the relationship between mutations of the PAX4 gene and various forms of diabetes mellitus (DM). PAX4 overexpression in adult islets stimulates β-cell proliferation and resistance to apoptosis. Taken together, the data indicate that PAX4 provides a potential target to develop new DM treatments aimed at reprogramming different cell types into insulin-producing cells and promoting their proliferation to replenish the β-cell pool lost during disease progression. The development of such methods requires knowledge of the molecular mechanisms that control expression of PAX4 and its target genes. The review summarizes the data on the structure and expression of the human PAX4 gene. Interactions of various transcription factors during differentiation of pancreatic cells and the formation of islets of Langerhans are described along with the role of PAX4 in the processes. Associations between mutations of human PAX4 and various DM forms were considered. A final part of the review examines the prospects for reprogramming cells of other types into insulin-producing cells and discusses the effects on PAX4- regulated signaling pathways as a means to develop new approaches to DM treatment.