Human Molecular Genetics Advance Access originally published online on October 21, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Molecular Genetics, 2003, Vol. 12, No. 24 3307-3314
DOI: 10.1093/hmg/ddg355
© 2003 Oxford University Press
Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas
1Endocrinology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain, 2Hormone Research Institute, University of California, San Francisco, CA, USA and 3Hormone and Metabolic Research Unit, Université Catholique de Louvain and Institute of Cellular Pathology, Brussels, Belgium
Received July 28, 2003; Accepted October 15, 2003
During pancreatic organogenesis endocrine cells arise from non self-renewing progenitors that express Ngn3. The precursors that give rise to Ngn3+ cells are presumably located within duct-like structures. However, the nature of such precursors is poorly understood. We show that, at E13–E18, the embryonic stage during which the major burst of ß-cell neogenesis takes place, pancreatic duct cells express Hnf1ß, the product of the maturity-onset diabetes of the young type 5 (MODY5) gene. Ngn3+ cells at this stage invariably cluster with mitotically competent Hnf1ß+ cells, and are often intercalated with these cells in the epithelium that lines the lumen of primitive ducts. We present several observations that collectively indicate that Hnf1ß+ cells are the immediate precursors of Ngn3+ cells. We furthermore show that Hnf1ß expression is markedly reduced in early pancreatic epithelial cells of Hnf6-deficient mice, in which formation of Ngn3+ cells is defective. These findings define a precursor cellular stage of the embryonic pancreas and place Hnf1ß in a genetic hierarchy that regulates the generation of pancreatic endocrine cells.
* To whom correspondence should be addressed at: Endocrinology, Hospital Clínic i Universitari, Villarroel 170, Barcelona-08036, Spain. Tel: +34 2275400(3028); Fax: +34 934516638; Email: jferrer{at}medicina.ub.es
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. J. Michels and T. M. Hagen Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent vitamin C transporter protein 1 Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1220 - C1227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Servitja, M. Pignatelli, M. A. Maestro, C. Cardalda, S. F. Boj, J. Lozano, E. Blanco, A. Lafuente, M. I. McCarthy, L. Sumoy, et al. Hnf1{alpha} (MODY3) Controls Tissue-Specific Transcriptional Programs and Exerts Opposed Effects on Cell Growth in Pancreatic Islets and Liver Mol. Cell. Biol., June 1, 2009; 29(11): 2945 - 2959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. McCarthy and A. T. Hattersley Learning From Molecular Genetics: Novel Insights Arising From the Definition of Genes for Monogenic and Type 2 Diabetes Diabetes, November 1, 2008; 57(11): 2889 - 2898. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Oliver-Krasinski and D. A. Stoffers On the origin of the {beta} cell Genes & Dev., August 1, 2008; 22(15): 1998 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J Welters, A. Oknianska, K. S Erdmann, G. U Ryffel, and N. G Morgan The protein tyrosine phosphatase-BL, modulates pancreatic {beta}-cell proliferation by interaction with the Wnt signalling pathway J. Endocrinol., June 1, 2008; 197(3): 543 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Edghill, R. A. Oram, M. Owens, K. L. Stals, L. W. Harries, A. T. Hattersley, S. Ellard, and C. Bingham Hepatocyte nuclear factor-1{beta} gene deletions--a common cause of renal disease Nephrol. Dial. Transplant., February 1, 2008; 23(2): 627 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Nelson, A. E. Schaffer, and M. Sander The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells Development, July 1, 2007; 134(13): 2491 - 2500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Lynn, S. B. Smith, M. E. Wilson, K. Y. Yang, N. Nekrep, and M. S. German Sox9 coordinates a transcriptional network in pancreatic progenitor cells PNAS, June 19, 2007; 104(25): 10500 - 10505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kitanaka, U. Sato, and T. Igarashi Regulation of human insulin, IGF-I, and multidrug resistance protein 2 promoter activity by hepatocyte nuclear factor (HNF)-1{beta} and HNF-1{alpha} and the abnormality of HNF-1{beta} mutants J. Endocrinol., January 1, 2007; 192(1): 141 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Maier, M. R. Dusing, and D. A. Wiginton Temporal Regulation of Enhancer Function in Intestinal Epithelium: A ROLE FOR ONECUT FACTORS J. Biol. Chem., October 27, 2006; 281(43): 32263 - 32271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Haumaitre, M. Fabre, S. Cormier, C. Baumann, A.-L. Delezoide, and S. Cereghini Severe pancreas hypoplasia and multicystic renal dysplasia in two human fetuses carrying novel HNF1{beta}/MODY5 mutations Hum. Mol. Genet., August 1, 2006; 15(15): 2363 - 2375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Luco, M. A. Maestro, N. del Pozo, W. M. Philbrick, P. P. de la Ossa, and J. Ferrer A Conditional Model Reveals That Induction of Hepatocyte Nuclear Factor-1{alpha} in Hnf1{alpha}-Null Mutant {beta}-Cells Can Activate Silenced Genes Postnatally, Whereas Overexpression Is Deleterious. Diabetes, August 1, 2006; 55(8): 2202 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. W. Harries, S. Ellard, A. Stride, The European MODY consortium, N. G. Morgan, and A. T. Hattersley Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes Hum. Mol. Genet., July 15, 2006; 15(14): 2216 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J Welters, S. Senkel, L. Klein-Hitpass, S. Erdmann, H. Thomas, L. W Harries, E. R Pearson, C. Bingham, A. T Hattersley, G. U Ryffel, et al. Conditional expression of hepatocyte nuclear factor-1{beta}, the maturity-onset diabetes of the young-5 gene product, influences the viability and functional competence of pancreatic {beta}-cells. J. Endocrinol., July 1, 2006; 190(1): 171 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Hattersley and E. R. Pearson Minireview: Pharmacogenetics and Beyond: The Interaction of Therapeutic Response, {beta}-Cell Physiology, and Genetics in Diabetes Endocrinology, June 1, 2006; 147(6): 2657 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E L Edghill, C Bingham, S Ellard, and A T Hattersley Mutations in hepatocyte nuclear factor-1{beta} and their related phenotypes J. Med. Genet., January 1, 2006; 43(1): 84 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bouwens and I. Rooman Regulation of Pancreatic Beta-Cell Mass Physiol Rev, October 1, 2005; 85(4): 1255 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Haumaitre, E. Barbacci, M. Jenny, M. O. Ott, G. Gradwohl, and S. Cereghini Lack of TCF2/vHNF1 in mice leads to pancreas agenesis PNAS, February 1, 2005; 102(5): 1490 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Salvador, R Sanmarti, A Garcia-Peiro, J R Rodriguez-Cros, J Munoz-Gomez, and J D Canete p53 Expression in rheumatoid and psoriatic arthritis synovial tissue and association with joint damage Ann Rheum Dis, February 1, 2005; 64(2): 183 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Thomas, S. Senkel, S. Erdmann, T. Arndt, G. Turan, L. Klein-Hitpass, and G. U. Ryffel Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4{alpha} and HNF1{beta} in a pancreatic {beta}-cell line Nucleic Acids Res., November 1, 2004; 32(19): e150 - e150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Briancon, A. Bailly, F. Clotman, P. Jacquemin, F. P. Lemaigre, and M. C. Weiss Expression of the {alpha}7 Isoform of Hepatocyte Nuclear Factor (HNF) 4 Is Activated by HNF6/OC-2 and HNF1 and Repressed by HNF4{alpha}1 in the Liver J. Biol. Chem., August 6, 2004; 279(32): 33398 - 33408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, C. Coffinier, M. K. Thomas, L. Gresh, G. Eddu, T. Manor, L. L. Levitsky, M. Yaniv, and D. B. Rhoads Selective Deletion of the Hnf1{beta} (MODY5) Gene in {beta}-Cells Leads to Altered Gene Expression and Defective Insulin Release Endocrinology, August 1, 2004; 145(8): 3941 - 3949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Pearson, M. K. Badman, C. R. Lockwood, P. M. Clark, S. Ellard, C. Bingham, and A. T. Hattersley Contrasting Diabetes Phenotypes Associated With Hepatocyte Nuclear Factor-1{alpha} and -1{beta} Mutations Diabetes Care, May 1, 2004; 27(5): 1102 - 1107. [Abstract] [Full Text] [PDF]
|
|