Foxa2 is required for the differentiation of pancreatic alpha-cells - PubMed (original) (raw)

. 2005 Feb 15;278(2):484-95.

doi: 10.1016/j.ydbio.2004.10.012.

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Foxa2 is required for the differentiation of pancreatic alpha-cells

Catherine S Lee et al. Dev Biol. 2005.

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Abstract

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.

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