Pax6 Is Required for Differentiation of Glucagon-Producing Alpha-Cells in Mouse Pancreas

Nature. 1997 May 22;387(6631):406-9. doi: 10.1038/387406a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Eye Proteins
  • Glucagon / biosynthesis
  • Homeodomain Proteins*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / embryology
  • Islets of Langerhans / metabolism
  • Mice
  • Mutation
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins
  • beta-Galactosidase / genetics

Substances

  • DNA-Binding Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Glucagon
  • beta-Galactosidase