%0 Journal Article
%T Pax4 and Arx Represent Crucial Regulators of the Development of the Endocrine Pancreas
%A Monica Courtney
%A Tamara Rabe
%A Patrick Collombat
%A Ahmed Mansouri
%J New Journal of Science
%D 2014
%R 10.1155/2014/981569
%X The development of the endocrine pancreas is under the control of highly orchestrated, cross-interacting transcription factors. Pancreas genesis is initiated by the emergence of a Pdx1/Ptf1a marked territory at the foregut/midgut junction. A small fraction of pancreatic fated cells activates the expression of the bHLH transcription factor Ngn3 triggering the endocrine cell program, thus giving rise to beta-, alpha-, delta-, PP-, and epsilon-cells, producing insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin, respectively. Two transcription factors, Pax4 and Arx, play a crucial role in differential endocrine cell subtype specification. They were shown to be necessary and sufficient to endow endocrine progenitors with either a beta- or alpha-cell destiny. Interestingly, whereas the forced expression of Arx in beta-cells converts these into cells exhibiting alpha- and PP-cell characteristics, the sole expression of Pax4 in alpha-cells promotes alpha-cell-neogenesis and the acquisition of beta-cell features, the resulting beta-like cells being capable of counteracting chemically induced diabetes. Gaining new insights into the molecular mechanisms controlling Pax4 and Arx expression in the endocrine pancreas may therefore pave new avenues for the therapy of diabetes. 1. Introduction The pancreas is composed of two distinct functional cell compartments. The major part comprises the exocrine tissue consisting of acinar cells secreting digestive enzymes and an intricate ductal system required for the transport of the digestive juice to the duodenum. The endocrine compartment is found scattered throughout the exocrine tissue and is organized into aggregates of hormone-producing cells forming functional units called islets of Langerhans [1, 2]. The mouse insulin-producing beta-cells are located in the core of the islets, whereas the remaining cells, expressing the hormones glucagon (alpha-cells), somatostatin (delta-cells), pancreatic polypeptide (PP-cells), and ghrelin (epsilon-cells), are detected in islet periphery [1, 3]. Insulin producing beta-cells are required to maintain glucose homeostasis. Indeed, their loss or malfunction eventually results in diabetes. Although medication aiming at controlling glycemia has improved, glycemic control is often difficult to achieve leading to side effects such as hypoglycemic episodes. Therefore, it is of fundamental interest to develop alternative therapeutic approaches, such as stem cell replacement, aiming at replenishing the beta-cell mass. Towards this goal, understanding the molecular mechanisms
%U http://www.hindawi.com/journals/njos/2014/981569/