spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 17 March 2004
doi: 10.1242/dev.01072

Development 131, 1717-1728 (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.01072v1
131/8/1717    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 Related articles in Development
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 Dunn, N. R.
Right arrow Articles by Bikoff, E. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dunn, N. R.
Right arrow Articles by Bikoff, E. K.

Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo

N. Ray Dunn, Stéphane D. Vincent, Leif Oxburgh, Elizabeth J. Robertson* and Elizabeth K. Bikoff

Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge MA 02138, USA

* Author for correspondence (e-mail: ejrobert{at}fas.harvard.edu)

Accepted 7 January 2004

TGFß/activin/Nodal receptors activate both Smad2 and Smad3 intracellular effector proteins. The functional activities of these closely related molecules have been extensively studied in cell lines. We show both are expressed in the early mouse embryo from the blastocyst stage onwards and mediate Foxh1-dependent activation of the Nodal autoregulatory enhancer in vitro. Genetic manipulation of their expression ratios reveals that Smad3 contributes essential signals at early post-implantation stages. Thus, loss of Smad3 in the context of one wild-type copy of Smad2 results in impaired production of anterior axial mesendoderm, while selective removal of both Smad2 and Smad3 from the epiblast additionally disrupts specification of axial and paraxial mesodermal derivatives. Finally, we demonstrate that Smad2;Smad3 double homozygous mutants entirely lack mesoderm and fail to gastrulate. Collectively, these results demonstrate that dose-dependent Smad2 and Smad3 signals cooperatively mediate cell fate decisions in the early mouse embryo.

Key words: Mesoderm induction, Smad2/3, Axis patterning, Nodal, Mouse


Related articles in Development:

An embryological double act

Development 2004 131: e801. [Full Text]  



This article has been cited by other articles:


Home page
 DevelopmentHome page
S. J. Arnold, U. K. Hofmann, E. K. Bikoff, and E. J. Robertson
Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse
Development, February 1, 2008; 135(3): 501 - 511.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Jia, Z. Ren, X. Li, Y. Zheng, and A. Meng
smad2 and smad3 Are Required for Mesendoderm Induction by Transforming Growth Factor- /Nodal Signals in Zebrafish
J. Biol. Chem., January 25, 2008; 283(4): 2418 - 2426.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. V. Esguerra, L. Nelles, L. Vermeire, A. Ibrahimi, A. D. Crawford, R. Derua, E. Janssens, E. Waelkens, P. Carmeliet, D. Collen, et al.
Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination
Development, December 15, 2007; 134(24): 4381 - 4393.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
R. L. C. Carvalho, F. Itoh, M.-J. Goumans, F. Lebrin, M. Kato, S. Takahashi, M. Ema, S. Itoh, M. van Rooijen, P. Bertolino, et al.
Compensatory signalling induced in the yolk sac vasculature by deletion of TGF receptors in mice
J. Cell Sci., December 15, 2007; 120(24): 4269 - 4277.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
R. Kitamura, T. Takahashi, N. Nakajima, K. Isodono, S. Asada, H. Ueno, T. Ueyama, T. Yoshikawa, H. Matsubara, and H. Oh
Stage-Specific Role of Endogenous Smad2 Activation in Cardiomyogenesis of Embryonic Stem Cells
Circ. Res., July 6, 2007; 101(1): 78 - 87.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. Puceat
TGF{beta} in the differentiation of embryonic stem cells
Cardiovasc Res, May 1, 2007; 74(2): 256 - 261.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. M. Shen
Nodal signaling: developmental roles and regulation
Development, March 15, 2007; 134(6): 1023 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
Y. Jeong, K. El-Jaick, E. Roessler, M. Muenke, and D. J. Epstein
A functional screen for sonic hedgehog regulatory elements across a 1 Mb interval identifies long-range ventral forebrain enhancers
Development, February 15, 2006; 133(4): 761 - 772.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
P. Lamba, M. M Santos, D. P Philips, and D. J Bernard
Acute regulation of murine follicle-stimulating hormone {beta} subunit transcription by activin A
J. Mol. Endocrinol., February 1, 2006; 36(1): 201 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
W. Ju, A. Ogawa, J. Heyer, D. Nierhof, L. Yu, R. Kucherlapati, D. A. Shafritz, and E. P. Bottinger
Deletion of Smad2 in Mouse Liver Reveals Novel Functions in Hepatocyte Growth and Differentiation
Mol. Cell. Biol., January 15, 2006; 26(2): 654 - 667.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. Chen, S. M. Ware, A. Sato, D. E. Houston-Hawkins, R. Habas, M. M. Matzuk, M. M. Shen, and C. W. Brown
The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo
Development, January 15, 2006; 133(2): 319 - 329.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. Chu, J. Ding, K. Jeays-Ward, S. M. Price, M. Placzek, and M. M. Shen
Non-cell-autonomous role for Cripto in axial midline formation during vertebrate embryogenesis
Development, December 15, 2005; 132(24): 5539 - 5551.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
P. Qiu, R. P. Ritchie, Z. Fu, D. Cao, J. Cumming, J. M. Miano, D.-Z. Wang, H. J. Li, and L. Li
Myocardin Enhances Smad3-Mediated Transforming Growth Factor-{beta}1 Signaling in a CArG Box-Independent Manner: Smad-Binding Element Is an Important cis Element for SM22{alpha} Transcription In Vivo
Circ. Res., November 11, 2005; 97(10): 983 - 991.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
L. Vallier, M. Alexander, and R. A. Pedersen
Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells
J. Cell Sci., October 1, 2005; 118(19): 4495 - 4509.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. James, A. J. Levine, D. Besser, and A. Hemmati-Brivanlou
TGF{beta}/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells
Development, March 15, 2005; 132(6): 1273 - 1282.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
N. R. Dunn, C. H. Koonce, D. C. Anderson, A. Islam, E. K. Bikoff, and E. J. Robertson
Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile
Genes & Dev., January 1, 2005; 19(1): 152 - 163.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
G. C. Chu, N. R. Dunn, D. C. Anderson, L. Oxburgh, and E. J. Robertson
Differential requirements for Smad4 in TGF{beta}-dependent patterning of the early mouse embryo
Development, August 1, 2004; 131(15): 3501 - 3512.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004