spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 1 Jun 2005
doi: 10.1242/dev.01870

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.01870v1
132/13/2969    most recent
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Collombat, P.
Right arrow Articles by Mansouri, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Collombat, P.
Right arrow Articles by Mansouri, A.

Research article

The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the {alpha}- and {beta}-cell lineages in the mouse endocrine pancreas


Patrick Collombat, Jacob Hecksher-Sørensen, Vania Broccoli, Jens Krull, Ilaria Ponte, Tabea Mundiger, Julian Smith, Peter Gruss, Palle Serup, and Ahmed Mansouri*
* Author for correspondence (e-mail: amansou{at}gwdg.de)

The specification of the different mouse pancreatic endocrine subtypes is determined by the concerted activities of transcription factors. However, the molecular mechanisms regulating endocrine fate allocation remain unclear. In the present study, we uncover the molecular consequences of the simultaneous depletion of Arx and Pax4 activity during pancreas development. Our findings reveal a so far unrecognized essential role of the paired-box-encoding Pax4 gene. Specifically, in the combined absence of Arx and Pax4, an early-onset loss of mature {alpha}- and {beta}-cells occurs in the endocrine pancreas, concomitantly with a virtually exclusive generation of somatostatin-producing cells. Furthermore, despite normal development of the PP-cells in the double-mutant embryos, an atypical expression of the pancreatic polypeptide (PP) hormone was observed in somatostatin-labelled cells after birth. Additional characterizations indicate that such an expression of PP was related to the onset of feeding, thereby unravelling an epigenetic control. Finally, our data provide evidence that both Arx and Pax4 act as transcriptional repressors that control the expression level of one another, thereby mediating proper endocrine fate allocation.


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
C. T. Fulp, G. Cho, E. D. Marsh, I. M. Nasrallah, P. A. Labosky, and J. A. Golden
Identification of Arx transcriptional targets in the developing basal forebrain
Hum. Mol. Genet., December 1, 2008; 17(23): 3740 - 3760.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Haumaitre, O. Lenoir, and R. Scharfmann
Histone Deacetylase Inhibitors Modify Pancreatic Cell Fate Determination and Amplify Endocrine Progenitors
Mol. Cell. Biol., October 15, 2008; 28(20): 6373 - 6383.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
T. Brun and B. R Gauthier
A focus on the role of Pax4 in mature pancreatic islet {beta}-cell expansion and survival in health and disease
J. Mol. Endocrinol., February 1, 2008; 40(2): 37 - 45.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
C. A. Fraker, S. Alvarez, P. Papadopoulos, J. Giraldo, W. Gu, C. Ricordi, L. Inverardi, and J. Dominguez-Bendala
Enhanced Oxygenation Promotes -Cell Differentiation In Vitro
Stem Cells, December 1, 2007; 25(12): 3155 - 3164.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. C. Jorgensen, J. Ahnfelt-Ronne, J. Hald, O. D. Madsen, P. Serup, and J. Hecksher-Sorensen
An Illustrated Review of Early Pancreas Development in the Mouse
Endocr. Rev., October 1, 2007; 28(6): 685 - 705.
[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
 Endocr. Rev.Home page
J. Gromada, I. Franklin, and C. B. Wollheim
{alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Endocr. Rev., February 1, 2007; 28(1): 84 - 116.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
L. C. Murtaugh
Pancreas and beta-cell development: from the actual to the possible
Development, February 1, 2007; 134(3): 427 - 438.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Mamin and J. Philippe
Activin A Decreases glucagon and arx Gene Expression in {alpha}-Cell Lines
Mol. Endocrinol., January 1, 2007; 21(1): 259 - 273.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
M. S. Gierl, N. Karoulias, H. Wende, M. Strehle, and C. Birchmeier
The Zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells
Genes & Dev., September 1, 2006; 20(17): 2465 - 2478.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005