Virtually all researchers on pancreatic and islet cell biology are familiar with the occasional sight of a single islet cell or small islets seemingly sprouting from the ducts of a section of adult pancreas. The incidence of such observations is amplified under a number of experimental or pathological conditions. For a long time, the obvious conclusion has been that islets might indeed be formed in or near the ducts, migrating at a later point to the acinar surroundings. BrdU labeling studies led to Bonner-Weir and colleagues to hypothesize that pancreatic regeneration in the partially pancreatectomized rat occurs through two pathways, namely: the self-replication of existing endocrine and exocrine cells; and the proliferation and differentiation of the ductal epithelium into new Read the rest of this entry »
Tags: Beta cell neogenesis, bone marrow cells, cell fusion, ductal origin hypothesis, ductal-specific carbonic anhydrase, NeuroD, New Beta Cells Arise from the Islet, Ngn3, Pax4, Pdx1, Pdx1 messenger RNA, proliferation and differentiation of the ductal epithelium, single islet cell
Little is known about the extracellular signals that drive beta cell specification from Ngn3 + progenitors. Animals lacking Nkx6.1 and Nkx2.2 have defects in beta cell formation. MafA has also been implicated in the terminal differentiation of beta cells, particularly in the beta cell-specific reactivation of Pdx1. However, several observations point to Pax4 as the main hallmark of beta cell differentiation: The knockout of this gene results in the total absence of beta cells, but not alpha cells; its expression peaks between e13.5 and e15.5, which coincides with the period of maximal differentiation of beta cell precursors ; and shortly after endocrine specification, Ngn3 colocalizes with Pax4 , which suggests that the latter may be one of the targets of the former. Read the rest of this entry »
Tags: alpha cells, aristaless related homeobox gene, C-terminal stretch of amino acids, delta cell, Foxa2 HNF3beta, hormone producing cells, Maf transcription factors, Ngn3 + progenitors, NK homeodomain family, Nkx6.1, Paired box-containing gene 4, Pax4, Pax6, winged-helix transcription factor Foxa2