Expression of HNF-4α (MODY1), HNF-1β (MODY5), and HNF-1α (MODY3) proteins in the developing mouse pancreas

• Published in: Gene Expression Patterns Vol. 8; no. 2; pp. 96 - 106
• Main Authors: Nammo, Takao, Yamagata, Kazuya, Tanaka, Toshiya, Kodama, Tatsuhiko, Sladek, Frances M., Fukui, Kenji, Katsube, Fumie, Sato, Yoshifumi, Miyagawa, Jun-ichiro, Shimomura, Iichiro
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2008
• Subjects: Amylase; Diabetes; Glucagon; HNF-1α; HNF-1β; HNF-4α; Insulin; Isl1; MODY1; MODY3; MODY5; Mouse; Ngn3; Nkx2.2; Pancreas; Pancreatic polypeptide; Pdx1; Somatostatin; Transcription factor; HNF-4α; Glucagon; Amylase; HNF-1α; HNF-1β; Pdx1; Isl1; Insulin; Nkx2.2; Pancreatic polypeptide; Mouse; MODY1; Diabetes; Ngn3; Somatostatin; MODY5; Pancreas; Transcription factor; MODY3
• ISSN: 1567-133X; 1872-7298
• DOI: 10.1016/j.modgep.2007.09.006

The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4α, HNF-1α, and HNF-1β, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3). Nature 384, 455–458; Yamagata, K., Furuta, H., Oda, N., Kaisaki, P.J., Menzel, S., Cox, N.J., et al., 1996b. Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1). Nature 384, 458–460; Horikawa, Y., Iwasaki, N., Hara, M., Furuta, H., Hinokio, Y., Cockburn, B.N. et al., 1997. Mutation in hepatocyte nuclear factor-1β gene (TCF2) associated with MODY. Nat. Genet. 17, 384–385]. Among these transcription factors, the pattern of HNF-4α expression during pancreatic differentiation remains largely unknown. We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1α and HNF-1β. We found considerable variation in the level of HNF-4α expression by the individual epithelial cells in the pancreatic buds on E9.5. HNF-4α and HNF-1β were initially expressed by Pdx1 + common progenitor cells and neurogenin3 + (Ngn3 +) endocrine precursor cells during the first transition, but expression of HNF-1β and either HNF-4α or HNF-1α became complementary around the end of the second transition (E15.5). In the mature pancreas, HNF-4α was expressed by glucagon-positive α-cells, insulin-positive β-cells, somatostatin-positive δ-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. Most of the HNF-4α + cells were also positive for HNF-1α, but HNF-4α expression in some non-β-cells was remarkably high, and this was not paralleled by high HNF-1α expression. These results indicate that the expression of MODY proteins in each of the pancreatic cell types is strictly regulated in accordance with the status of differentiation during pancreatic organogenesis.