Foxa2 is required for the differentiation of pancreatic alpha-cells

Lee, C. S.; Sund, N. J.; Behr, Rudiger; Herrera, Pedro Luis; Kaestner, K. H.

doi:10.1016/j.ydbio.2004.10.012

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Title		Foxa2 is required for the differentiation of pancreatic alpha-cells
Authors		Lee, C. S. Sund, N. J. Behr, Rudiger Herrera, Pedro Luis Kaestner, K. H.
Published in		Developmental Biology. 2005, vol. 278, no. 2, p. 484-495
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
Identifiers		DOI: 10.1016/j.ydbio.2004.10.012 PMID: 15680365
Full text		Article - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Research group		Types cellulaires pancréatiques pendant l'ontogénèse (522)
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 https://archive-ouverte.unige.ch/unige:8854