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


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 17 November 2004
doi: 10.1242/dev.01535

Development 131, 6163-6174 (2004)
Published by The Company of Biologists 2004
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.01535v1
131/24/6163    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 Harmon, E. B.
Right arrow Articles by Kim, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harmon, E. B.
Right arrow Articles by Kim, S. K.

GDF11 modulates NGN3+ islet progenitor cell number and promotes ß-cell differentiation in pancreas development

Erin B. Harmon1,{dagger}, Åsa A. Apelqvist1,*,{dagger}, Nora G. Smart1, Xueying Gu1, Douglas H. Osborne1 and Seung K. Kim1,2,{ddagger}

1 Department of Developmental Biology, Stanford University, Stanford, CA 94305-5329, USA
2 Department of Medicine (Oncology Division), Stanford University, Stanford, CA 94305-5329, USA

{ddagger} Author for correspondence (e-mail: seungkim{at}cmgm.stanford.edu)

Accepted 21 September 2004

Identification of endogenous signals that regulate expansion and maturation of organ-specific progenitor cells is a major goal in studies of organ development. Here we provide evidence that growth differentiation factor 11 (GDF11), a member of the TGF-ß ligand family, governs the number and maturation of islet progenitor cells in mouse pancreas development. Gdf11 is expressed in embryonic pancreatic epithelium during formation of islet progenitor cells that express neurogenin 3. Mice deficient for Gdf11 harbor increased numbers of NGN3+ cells, revealing that GDF11 negatively regulates production of islet progenitor cells. Despite a marked expansion of these NGN3+ islet progenitors, mice lacking Gdf11 have reduced ß-cell numbers and evidence of arrested ß-cell development, indicating that GDF11 is also required for ß-cell maturation. Similar precursor and islet cell phenotypes are observed in mice deficient for SMAD2, an intracellular signaling factor activated by TGF-ß signals. Our data suggest that Gdf11 and Smad2 regulate islet cell differentiation in parallel to the Notch pathway, which previously has been shown to control development of NGN3+ cells. Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development.

Key words: Gdf11, TGF-ß, Pancreas, Islet of Langerhans, Insulin, Stem cell




This article has been cited by other articles:


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
 EndocrinologyHome page
A. L. Schneyer, Y. Sidis, A. Gulati, J. L. Sun, H. Keutmann, and P. A. Krasney
Differential Antagonism of Activin, Myostatin and Growth and Differentiation Factor 11 by Wild-Type and Mutant Follistatin
Endocrinology, September 1, 2008; 149(9): 4589 - 4595.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Kondas, G. Szlama, M. Trexler, and L. Patthy
Both WFIKKN1 and WFIKKN2 Have High Affinity for Growth and Differentiation Factors 8 and 11
J. Biol. Chem., August 29, 2008; 283(35): 23677 - 23684.
[Abstract] [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
 Stem CellsHome page
I. Serafimidis, I. Rakatzi, V. Episkopou, M. Gouti, and A. Gavalas
Novel Effectors of Directed and Ngn3-Mediated Differentiation of Mouse Embryonic Stem Cells into Endocrine Pancreas Progenitors
Stem Cells, January 1, 2008; 26(1): 3 - 16.
[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
 Proc. Natl. Acad. Sci. USAHome page
I. C. Rulifson, S. K. Karnik, P. W. Heiser, D. ten Berge, H. Chen, X. Gu, M. M. Taketo, R. Nusse, M. Hebrok, and S. K. Kim
Wnt signaling regulates pancreatic beta cell proliferation
PNAS, April 10, 2007; 104(15): 6247 - 6252.
[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
 Am. J. Physiol. Endocrinol. Metab.Home page
D. M. Simeone, L. Zhang, M. K. Treutelaar, L. Zhang, K. Graziano, C. D. Logsdon, and C. F. Burant
Islet hypertrophy following pancreatic disruption of Smad4 signaling
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1305 - E1316.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
N. Bardeesy, K.-h. Cheng, J. H. Berger, G. C. Chu, J. Pahler, P. Olson, A. F. Hezel, J. Horner, G. Y. Lauwers, D. Hanahan, et al.
Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer.
Genes & Dev., November 15, 2006; 20(22): 3130 - 3146.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
M. Ta, Y. Choi, F. Atouf, C. H. Park, and N. Lumelsky
The Defined Combination of Growth Factors Controls Generation of Long-Term-Replicating Islet Progenitor-Like Cells from Cultures of Adult Mouse Pancreas
Stem Cells, July 1, 2006; 24(7): 1738 - 1749.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S.-J. Lee, L. A. Reed, M. V. Davies, S. Girgenrath, M. E. P. Goad, K. N. Tomkinson, J. F. Wright, C. Barker, G. Ehrmantraut, J. Holmstrom, et al.
Regulation of muscle growth by multiple ligands signaling through activin type II receptors
PNAS, December 13, 2005; 102(50): 18117 - 18122.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
G. Ge, D. R. Hopkins, W.-B. Ho, and D. S. Greenspan
GDF11 Forms a Bone Morphogenetic Protein 1-Activated Latent Complex That Can Modulate Nerve Growth Factor-Induced Differentiation of PC12 Cells
Mol. Cell. Biol., July 15, 2005; 25(14): 5846 - 5858.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004