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Scientific article
English

Foxa2 is required for the differentiation of pancreatic alpha-cells

Published inDevelopmental biology, vol. 278, no. 2, p. 484-495
Publication date2005
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.

Keywords
  • Animals
  • Base Sequence
  • Cell Differentiation
  • Chromosomes, Artificial, Yeast
  • DNA Primers
  • DNA-Binding Proteins/deficiency/ genetics
  • Embryonic Development/genetics
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Genotype
  • Hepatocyte Nuclear Factor 3-beta
  • Hypoglycemia/genetics
  • Islets of Langerhans/ embryology
  • Mice
  • Mice, Knockout
  • Nuclear Proteins/deficiency/ genetics
  • Pancreas/ embryology
  • Reproducibility of Results
  • Transcription Factors/deficiency/ genetics
Citation (ISO format)
LEE, C. S. et al. Foxa2 is required for the differentiation of pancreatic alpha-cells. In: Developmental biology, 2005, vol. 278, n° 2, p. 484–495. doi: 10.1016/j.ydbio.2004.10.012
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ISSN of the journal0012-1606
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