First Author | Lee CS | Year | 2005 |
Journal | Dev Biol | Volume | 278 |
Issue | 2 | Pages | 484-95 |
PubMed ID | 15680365 | Mgi Jnum | J:96332 |
Mgi Id | MGI:3530180 | Doi | 10.1016/j.ydbio.2004.10.012 |
Citation | Lee CS, et al. (2005) Foxa2 is required for the differentiation of pancreatic alpha-cells. Dev Biol 278(2):484-95 |
abstractText | The differentiation of insulin-producing beta-cells has been investigated in great detail; however, little is known about the factors that delineate the second-most abundant endocrine lineage, the glucagon-producing alpha-cell. Here we utilize a novel YAC-based Foxa3Cre transgene to delete the winged helix transcription factor Foxa2 (formerly HNF-3beta) in the pancreatic primordium during midgestation. The resulting Foxa2(loxP/loxP); Foxa3Cre mice are severely hypoglycemic and die within the first week of life. Mutant mice are hypoglucagonemic secondary to a 90% reduction of glucagon expression. While the number of mature glucagon-positive alpha-cells is dramatically reduced, specification of alpha-cell progenitors is not affected by Foxa2 deficiency. By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation. |