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Foxa2 is required for the differentiation of pancreatic alpha-cells

Lee, C. S.
Sund, N. J.
Behr, Rudiger
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 AnimalsBase SequenceCell DifferentiationChromosomes, Artificial, YeastDNA PrimersDNA-Binding Proteins/deficiency/ geneticsEmbryonic Development/geneticsGene DeletionGene Expression Regulation, DevelopmentalGenotypeHepatocyte Nuclear Factor 3-betaHypoglycemia/geneticsIslets of Langerhans/ embryologyMiceMice, KnockoutNuclear Proteins/deficiency/ geneticsPancreas/ embryologyReproducibility of ResultsTranscription Factors/deficiency/ genetics
PMID: 15680365
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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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

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Deposited on : 2010-07-12

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