PAX6 IS REQUIRED FOR DIFFERENTIATION OF GLUCAGON-PRODUCING ALPHA-CELLS IN MOUSE PANCREAS

The functional unit of the endocrine pancreas is the islet of Langerha ns. Islets are nested within the exocrine tissue of the pancreas and a re composed of alpha-, beta-, delta- and gamma-cells(1). P-Cells produ ce insulin and form the core of the islet, whereas alpha-, delta- and gamma-cells are arranged at the periphery of the islet and secrete glu cagon, somatostatin and a pancreatic polypeptide, respectively. Little is known about the molecular and genetic factors regulating the linea ge of the different endocrine cells. Pancreas development is known to be abolished in Pdx1-mutant mice(2) and Pax4 mutants lack insulin-prod ucing beta-cells(3). Here we show that the paired-box gene Pax6 is exp ressed during the early stages of pancreatic development and in mature endocrine cells. The pancreas of Pax6 homozygous mutant mice lack glu cagon-producing cells, suggesting that Pax6 is essential for the diffe rentiation of alpha-cells. As mice lacking Pax4 and Pax6 fail to devel op any mature endocrine cells, we conclude that both Pax genes are req uired for endocrine fate in the pancreas.