Embryonic endocrine pancreas and mature β cells acquire α and PP cell phenotypes upon Arx misexpression
J. Clin. Invest. Patrick Collombat, et al. 117:961 doi:10.1172/JCI29115 [Go to this article.]

Figure 4
Favoring of the glucagon- and PP-producing cell fates at the expense of the β and δ cell lineages during endocrine pancreas morphogenesis in cArxOE::Pax6Cre or cArxOE::Pdx1Cre pancreata. (A–DD) Representative pancreatic sections costained with the indicated antibody combinations, at the indicated embryonic stages. A quantification of the endocrine modifications between the Cre-negative and Cre-positive mice, estimated by the 1-tailed Student’s t test, is provided in percent under each set of pictures in matching colors (n ≥ 3, P < 0.05). A clear loss of β (A–C) and δ (D–F and V–X) cells is evidenced in animals misexpressing Arx. Concurrently, an increase in glucagon (A–U and Y–DD) or PP (G–I) cell content occurs, with Arx being detected in most of the endocrine tissue (J–L), but also in exocrine cells in the case of cArxOE::Pdx1Cre (L, arrows). The numbers of cells labeled with the β cell–specific markers Nkx6.1 (M–O), Pdx1 (P–R), and Glut2 (S–U) are drastically reduced in Cre-positive mice. Similarly, the expression of CART, normally marking δ cells, is profoundly diminished (V–X), whereas the expression of the α cell–specific gene Brn4 is augmented (Y–AA). The content in cells positive for the endocrine marker Pax6 is not affected (BB–DD). Each picture is representative of 3–8 animals from different litters. U, unchanged. Original magnification, ×40.