Table of Contents
New Journal of Science
Volume 2014, Article ID 981569, 6 pages
http://dx.doi.org/10.1155/2014/981569
Review Article

Pax4 and Arx Represent Crucial Regulators of the Development of the Endocrine Pancreas

1Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, 06108 Nice, France
2Inserm U1091, IBV, Diabetes Genetics Team, 06108 Nice, France
3JDRF, 26 Broadway, NY 10004, USA
4Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemsitry, Am Fassberg 11, 37077 Goettingen, Germany
5Genome and Stem Cell Center, GENKOK, Erciyes University, Kayseri, Turkey
6Department of Clinical Neurophysiology, University of Goettingen, Robert-Koch-Straße 40, 37075 Goettingen, Germany

Received 10 April 2014; Accepted 12 May 2014; Published 29 May 2014

Academic Editor: Hui-Qi Qu

Copyright © 2014 Monica Courtney et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.