Skip Navigation



Human Molecular Genetics Advance Access published online on October 21, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg355
© 2003 by Oxford University Press
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
12/24/3307    most recent
ddg355v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Maestro, M. A.
Right arrow Articles by Ferrer, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maestro, M. A.
Right arrow Articles by Ferrer, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

©2003 Oxford University Press

Article

Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas

Miguel A. Maestro 1, Sylvia F. Boj 1, Reini F. Luco 1, Christophe E. Pierreux 2, Judit Cabedo 1, Joan M. Servitja 1, Michael German 2, Guy G. Rousseau 3, Frédéric P. Lemaigre 3, and Jorge Ferrer 4*

1 Endocrinology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
2 Hormone Research Institute, University of California, San Francisco, Ca
3 Hormone and Metabolic Research Unit, Université Catholique de Louvain and Institute of Cellular Pathology, Brussels, Belgium
4 Endocrinology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic i Universitari, Villarroel 170, Barcelona, 08036, Spain

* To whom correspondence should be addressed. E-mail: jferrer{at}medicina.ub.es.


  Abstract

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 now show that at E13-E18, the embryonic stage during which the major burst of {beta}-cell neogenesis takes place, pancreatic duct cells express Hnf1{beta}, the product of the maturity onset diabetes of the young Type 5 (MODY5) gene. Ngn3+ cells at this stage invariably cluster with mitotically competent Hnf1{beta}+ 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 Hnf1{beta}+ cells are the immediate precursors of Ngn3+ cells. We furthermore show that Hnf1{beta} 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 Hnf1{beta} in a genetic hierarchy that regulates the generation of pancreatic endocrine cells.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
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]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 DiabetesHome page
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]

Home page
 Genes Dev.Home page
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]

Home page
 J EndocrinolHome page
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]

Home page
 Nephrol Dial TransplantHome page
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]

Home page
 DevelopmentHome page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 J EndocrinolHome page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Hum Mol GenetHome page
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]

Home page
 DiabetesHome page
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]

Home page
 Hum Mol GenetHome page
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]

Home page
 J EndocrinolHome page
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]

Home page
 EndocrinologyHome page
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]

Home page
 J. Med. Genet.Home page
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]

Home page
 Physiol. Rev.Home page
L. Bouwens and I. Rooman
Regulation of Pancreatic Beta-Cell Mass
Physiol Rev, October 1, 2005; 85(4): 1255 - 1270.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 Ann Rheum DisHome page
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]

Home page
 Nucleic Acids ResHome page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 EndocrinologyHome page
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]

Home page
 Diabetes CareHome page
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]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.