title: Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas.
abstract: The functional unit of the endocrine pancreas is the islet of Langerhans. Islets are nested within the exocrine tissue of the pancreas and are composed of alpha-, beta-, delta- and gamma-cells. beta-Cells produce insulin and form the core of the islet, whereas alpha-, delta- and gamma-cells are arranged at the periphery of the islet and secrete glucagon, somatostatin and a pancreatic polypeptide, respectively. Little is known about the molecular and genetic factors regulating the lineage of the different endocrine cells. Pancreas development is known to be abolished in Pdx1-mutant mice and Pax4 mutants lack insulin-producing beta-cells. Here we show that the paired-box gene Pax6 is expressed during the early stages of pancreatic development and in mature endocrine cells. The pancreas of Pax6 homozygous mutant mice lack glucagon-producing cells, suggesting that Pax6 is essential for the differentiation of alpha-cells. As mice lacking Pax4 and Pax6 fail to develop any mature endocrine cells, we conclude that both Pax genes are required for endocrine fate in the pancreas.
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: St-Onge
authors.forename: B
authors.initials: B
authors.lastname: Sosa-Pineda
authors.forename: K
authors.initials: K
authors.lastname: Chowdhury
authors.forename: A
authors.initials: A
authors.lastname: Mansouri
authors.forename: P
authors.initials: P
authors.lastname: Gruss
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins; D005934:Glucagon / Q000096:biosynthesis; D018398:Homeodomain Proteins; D007515:Islets of Langerhans / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D005934:Glucagon; D001616:beta-Galactosidase