Characterization of a role of protein arginine N-methyltransferase 1 in the pancreas development

Abstract

Pancreatic progenitor cells are differentiated into endocrine cells through the expression of Neurogenin3 (Neurog3 or Ngn3). Here, we present the evidence that Prmt1 (Protein arginine N-methyltransferase 1) is essential for Neurog3 protein regulation and subsequent endocrine cell commitment. Specifically, Prmt1 promotes ubiquitin-proteasome mediated degradation of Neurog3 protein in endocrine progenitors and subsequent induces them delaminate to mesenchyme and commit to endocrine cell. Therefore, in the absence of Prmt1, Neurog3+ endocrine progenitors continue to maintain their Neurog3 expression are not able to delaminate and commit to hormone producing endocrine cells. In addition, prolongation of Neurog3 protein causes secondary transition failure and consequently shows neonatal diabetic phenotype due to insulin insufficiency.