|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
1 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
2 Division of Developmental Biology, Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
*Author for correspondence (e-mail: mwhitman{at}hms.harvard.edu)
Accepted May 16, 2001
Signaling by activin-like ligands is important for induction and patterning of mesoderm and endoderm. We have used an antibody that specifically recognizes the phosphorylated and activated form of Smad2, an intracellular transducer of activin-like ligands, to examine how this signaling pathway patterns the early mesendoderm. In contrast to the simple expectation that activin-like signaling should be highest on the dorsal side of the gastrula stage embryo, we have found that while Smad2 phosphorylation is highest dorsally before gastrulation, signaling is attenuated dorsally and is highest on the ventral side by mid-gastrulation. Early dorsal initiation of Smad2 phosphorylation results from cooperation between the vegetally localized maternal transcription factor VegT and dorsally localized ß-catenin. The subsequent ventral appearance of Smad2 phosphorylation is dependent on VegT, but not on signaling from the dorsal side. Dorsal attenuation of Smad2 phosphorylation during gastrulation is mediated by early dorsal expression of feedback inhibitors of activin-like signals.
In addition to regulation of Smad2 phosphorylation by the expression of activin-like ligands and their antagonists, the responsiveness of embryonic cells to activin-like ligands is also temporally regulated. Ectopic Vg1, Xnr1 and derrière all fail to activate Smad2 phosphorylation until after the midblastula transition, and the onset of responsiveness to these ligands is independent of transcription. Furthermore, the timing of cellular responsiveness differs for Xnr1 and derrière, and these distinct temporal patterns of responsiveness can be correlated with their distinctive phenotypic effects. These observations suggest that the timing of endogenous activin-like signaling is a determinant of patterning in the early Xenopus embryo.
Key words: Smad, Phosphorylation, TGFß, Nodal, Mesoderm induction, Signal transduction, Xenopus laevis
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. F. Schier Nodal Morphogens Cold Spring Harb Perspect Biol, November 1, 2009; 1(5): a003459 - a003459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Batut, B. Schmierer, J. Cao, L. A. Raftery, C. S. Hill, and M. Howell Two highly related regulatory subunits of PP2A exert opposite effects on TGF-{beta}/Activin/Nodal signalling Development, September 1, 2008; 135(17): 2927 - 2937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Keller and D. Shook Dynamic determinations: patterning the cell behaviours that close the amphibian blastopore Phil Trans R Soc B, April 12, 2008; 363(1495): 1317 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Anderson, A. L. Goldberg, and M. Whitman Identification of a Novel Pool of Extracellular Pro-myostatin in Skeletal Muscle J. Biol. Chem., March 14, 2008; 283(11): 7027 - 7035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Saka, A. I. Hagemann, O. Piepenburg, and J. C. Smith Nuclear accumulation of Smad complexes occurs only after the midblastula transition in Xenopus Development, December 1, 2007; 134(23): 4209 - 4218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chang and R. M. Harland Neural induction requires continued suppression of both Smad1 and Smad2 signals during gastrulation Development, November 1, 2007; 134(21): 3861 - 3872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogata, J. Morokuma, T. Hayata, G. Kolle, C. Niehrs, N. Ueno, and K. W.Y. Cho TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis Genes & Dev., July 15, 2007; 21(14): 1817 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Shen Nodal signaling: developmental roles and regulation Development, March 15, 2007; 134(6): 1023 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Steiner, M. J. Engleka, Q. Lu, E. C. Piwarzyk, S. Yaklichkin, J. L. Lefebvre, J. W. Walters, L. Pineda-Salgado, P. A. Labosky, and D. S. Kessler FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development Development, December 15, 2006; 133(24): 4827 - 4838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Heasman Patterning the early Xenopus embryo. Development, April 1, 2006; 133(7): 1205 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Onuma, C.-Y. Yeo, and M. Whitman XCR2, one of three Xenopus EGF-CFC genes, has a distinct role in the regulation of left-right patterning Development, January 15, 2006; 133(2): 237 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Birsoy, M. Kofron, K. Schaible, C. Wylie, and J. Heasman Vg1 is an essential signaling molecule in Xenopus development Development, January 1, 2006; 133(1): 15 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jullien and J. Gurdon Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction Genes & Dev., November 15, 2005; 19(22): 2682 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Houston and C. Wylie Maternal Xenopus Zic2 negatively regulates Nodal-related gene expression during anteroposterior patterning Development, November 1, 2005; 132(21): 4845 - 4855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Daniels, K. Shimizu, A. M. Zorn, and S.-i. Ohnuma Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm formation Development, November 15, 2004; 131(22): 5613 - 5626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kofron, H. Puck, H. Standley, C. Wylie, R. Old, M. Whitman, and J. Heasman New roles for FoxH1 in patterning the early embryo Development, October 15, 2004; 131(20): 5065 - 5078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Kunwar, S. Zimmerman, J. T. Bennett, Y. Chen, M. Whitman, and A. F. Schier Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction Development, December 1, 2003; 130(23): 5589 - 5599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Hiratani, N. Yamamoto, T. Mochizuki, S.-y. Ohmori, and M. Taira Selective degradation of excess Ldb1 by Rnf12/RLIM confers proper Ldb1 expression levels and Xlim-1/Ldb1 stoichiometry in Xenopus organizer functions Development, September 1, 2003; 130(17): 4161 - 4175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Dougan, R. M. Warga, D. A. Kane, A. F. Schier, and W. S. Talbot The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm Development, May 1, 2003; 130(9): 1837 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Howell, G. J. Inman, and C. S. Hill A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements Development, March 8, 2003; 129(12): 2823 - 2834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Cheng, F. Olale, J. T. Bennett, A. H. Brivanlou, and A. F. Schier EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1 Genes & Dev., January 1, 2003; 17(1): 31 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Xanthos, M. Kofron, Q. Tao, K. Schaible, C. Wylie, and J. Heasman The roles of three signaling pathways in the formation and function of the Spemann Organizer Development, September 1, 2002; 129(17): 4027 - 4043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Eimon and R. M. Harland Effects of heterodimerization and proteolytic processing on Derriere and Nodal activity: implications for mesoderm induction in Xenopus Development, January 7, 2002; 129(13): 3089 - 3103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-Y. Bourillot, N. Garrett, and J. B. Gurdon A changing morphogen gradient is interpreted by continuous transduction flow Development, January 5, 2002; 129(9): 2167 - 2180. [Abstract] [Full Text] [PDF]
|
|
