|
 |
|
|||||||
|
|||||||||
Diabetes 51:2546-2551, 2002
© 2002 by the American Diabetes Association, Inc.
Foxa2 Controls Pdx1 Gene Expression in Pancreatic ß-Cells In Vivo
1 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
2 Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
3 Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
4 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a cascade of gene activation events controlled by various transcription factors. Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3ß) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. Pdx1 is also essential for the maintenance of glucose homeostasis, as its human orthologue, IPF-1, is mutated in a subset of patients with early-onset type 2 diabetes (MODY4). To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic ß-cell differentiation, we used conditional gene ablation of Foxa2 in mice. We demonstrated that the deletion of Foxa2 in ß-cell-specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated ß-cell.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Baroukh, M. A. Ravier, M. K. Loder, E. V. Hill, A. Bounacer, R. Scharfmann, G. A. Rutter, and E. Van Obberghen MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic beta-Cell Lines J. Biol. Chem., July 6, 2007; 282(27): 19575 - 19588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Miele, G. A. Raciti, A. Cassese, C. Romano, F. Giacco, F. Oriente, F. Paturzo, F. Andreozzi, A. Zabatta, G. Troncone, et al. PED/PEA-15 Regulates Glucose-Induced Insulin Secretion by Restraining Potassium Channel Expression in Pancreatic {beta}-Cells Diabetes, March 1, 2007; 56(3): 622 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. McKinnon, M. A. Ravier, and G. A. Rutter FoxO1 Is Required for the Regulation of Preproglucagon Gene Expression by Insulin in Pancreatic {alpha}TC1-9 Cells J. Biol. Chem., December 22, 2006; 281(51): 39358 - 39369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Z. Vatamaniuk, R. K. Gupta, K. A. Lantz, N. M. Doliba, F. M. Matschinsky, and K. H. Kaestner Foxa1-Deficient Mice Exhibit Impaired Insulin Secretion due to Uncoupled Oxidative Phosphorylation. Diabetes, October 1, 2006; 55(10): 2730 - 2736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Eto, V. Kaur, and M. K. Thomas Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1 Endocrinology, June 1, 2006; 147(6): 2923 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. De Leon, C. Farzad, M. F. Crutchlow, J. Brestelli, J. Tobias, K. H. Kaestner, and D. A. Stoffers Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment Physiol Genomics, January 12, 2006; 24(2): 133 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Volinic, J. H. Lee, K. Eto, V. Kaur, and M. K. Thomas Overexpression of the Coactivator Bridge-1 Results in Insulin Deficiency and Diabetes Mol. Endocrinol., January 1, 2006; 20(1): 167 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E Garnett, P. Chapman, J. A Chambers, I. D Waddell, and D. S W Boam Differential gene expression between Zucker Fatty rats and Zucker Diabetic Fatty rats: a potential role for the immediate-early gene Egr-1 in regulation of beta cell proliferation J. Mol. Endocrinol., August 1, 2005; 35(1): 13 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Moriscot, F. de Fraipont, M.-J. Richard, M. Marchand, P. Savatier, D. Bosco, M. Favrot, and P.-Y. Benhamou Human Bone Marrow Mesenchymal Stem Cells Can Express Insulin and Key Transcription Factors of the Endocrine Pancreas Developmental Pathway upon Genetic and/or Microenvironmental Manipulation In Vitro Stem Cells, April 1, 2005; 23(4): 594 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, X. Cao, L.-X. Li, P. L. Brubaker, H. Edlund, and D. J. Drucker {beta}-Cell Pdx1 Expression Is Essential for the Glucoregulatory, Proliferative, and Cytoprotective Actions of Glucagon-Like Peptide-1 Diabetes, February 1, 2005; 54(2): 482 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Holz and O. G. Chepurny Diabetes Outfoxed by GLP-1? Sci. Signal., January 25, 2005; 2005(268): pe2 - pe2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Behr, J. Brestelli, J. T. Fulmer, N. Miyawaki, T. R. Kleyman, and K. H. Kaestner Mild Nephrogenic Diabetes Insipidus Caused by Foxa1 Deficiency J. Biol. Chem., October 1, 2004; 279(40): 41936 - 41941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. MELLOUL Transcription Factors in Islet Development and Physiology: Role of PDX-1 in Beta-Cell Function Ann. N.Y. Acad. Sci., April 1, 2004; 1014(1): 28 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gerrish, J. C. Van Velkinburgh, and R. Stein Conserved Transcriptional Regulatory Domains of the pdx-1 Gene Mol. Endocrinol., March 1, 2004; 18(3): 533 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Md. R. Abid, S. Guo, T. Minami, K. C. Spokes, K. Ueki, C. Skurk, K. Walsh, and W. C. Aird Vascular Endothelial Growth Factor Activates PI3K/Akt/Forkhead Signaling in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): 294 - 300. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-S. Annicotte, E. Fayard, G. H. Swift, L. Selander, H. Edlund, T. Tanaka, T. Kodama, K. Schoonjans, and J. Auwerx Pancreatic-Duodenal Homeobox 1 Regulates Expression of Liver Receptor Homolog 1 during Pancreas Development Mol. Cell. Biol., October 1, 2003; 23(19): 6713 - 6724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wolfrum, D. Besser, E. Luca, and M. Stoffel From the Cover: Insulin regulates the activity of forkhead transcription factor Hnf-3{beta}/Foxa-2 by Akt-mediated phosphorylation and nuclear/cytosolic localization PNAS, September 30, 2003; 100(20): 11624 - 11629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Samaras, L. Zhao, A. Means, E. Henderson, T.-a. Matsuoka, and R. Stein The Islet beta Cell-enriched RIPE3b1/Maf Transcription Factor Regulates pdx-1 Expression J. Biol. Chem., March 28, 2003; 278(14): 12263 - 12270. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |