The forkhead gene family, named after the founding gene member in Drosophila, is characterized by a unique DNA-binding domain. This so-called forkhead box encodes a winged-helix DNA-binding motif, the name of which describes the structure of the domain when bound to DNA. The three Fox (forkhead box) group A genes, Foxa1, Foxa2 and Foxa3, are expressed in embryonic endoderm, the germ layer that gives rise to the digestive system, and contribute to the specification of the pancreas and the regulation of glucose homoeostasis. Deletion of the Foxa2 gene in pancreatic β-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). Molecular analyses have demonstrated that Foxa2 is an important regulator of the genes encoding Sur1, Kir6.2 and Schad (short chain L-3-hydroxyacyl-CoA dehydrogenase), mutation of which causes PHHI in humans. Foxa1 was shown to be an essential activator of glucagon gene expression in vivo. An additional winged-helix protein, Foxo1, contributes to pancreatic β-cell function by regulating the Pdx1 gene, which is required for pancreatic development in cooperation with Foxa2.
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March 2005
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Review Article|
February 18 2005
Winged-helix transcription factors and pancreatic development
Kristen A. LANTZ
;
Kristen A. LANTZ
*Department of Genetics, University of Pennsylvania Medical School, 560 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104, U.S.A.
†Penn Diabetes Center, University of Pennsylvania Medical School, 501 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104, U.S.A.
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Klaus H. KAESTNER
*Department of Genetics, University of Pennsylvania Medical School, 560 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104, U.S.A.
†Penn Diabetes Center, University of Pennsylvania Medical School, 501 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104, U.S.A.
Correspondence: Dr Klaus H. Kaestner, Department of Genetics, University of Pennsylvania Medical School, 560 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104, U.S.A. (email kaestner@mail.med.upenn.edu).
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Clin Sci (Lond) (2005) 108 (3): 195–204.
Article history
Received:
October 25 2004
Revision Received:
November 22 2004
Accepted:
January 05 2005
Accepted Manuscript online:
January 05 2005
Citation
Kristen A. LANTZ, Klaus H. KAESTNER; Winged-helix transcription factors and pancreatic development. Clin Sci (Lond) 1 March 2005; 108 (3): 195–204. doi: https://doi.org/10.1042/CS20040309
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