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 27 April 2005
doi: 10.1242/dev.01842

Development 132, 2599-2609 (2005)
Published by The Company of Biologists 2005
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
dev.01842v1
132/11/2599    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 Lickert, H.
Right arrow Articles by Rossant, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lickert, H.
Right arrow Articles by Rossant, J.

Dissecting Wnt/ß-catenin signaling during gastrulation using RNA interference in mouse embryos

Heiko Lickert1,*, Brian Cox1,4, Christian Wehrle2, Makoto M. Taketo3, Rolf Kemler2 and Janet Rossant1,4,{dagger}

1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada
2 Max-Planck Institute of Immunobiology, Department of Molecular Embryology, Freiburg 79108, Germany
3 Kyoto University Graduate School of Medicine, Department of Pharmacology, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
4 University of Toronto, Department of Medical Genetics and Microbiology, Toronto M5S 1A8, Canada

{dagger} Author for correspondence (e-mail: rossant{at}mshri.on.ca)

Accepted 30 March 2005

Differential gene regulation integrated in time and space drives developmental programs during embryogenesis. To understand how the program of gastrulation is regulated by Wnt/ß-catenin signaling, we have used genome-wide expression profiling of conditional ß-catenin mutant embryos. Known Wnt/ß-catenin target genes, known components of other signaling pathways, as well as a number of uncharacterized genes were downregulated in these mutants. To further narrow down the set of differentially expressed genes, we used whole-mount in situ screening to associate gene expression with putative domains of Wnt activity. Several potential novel target genes were identified by this means and two, Grsf1 and Fragilis2, were functionally analyzed by RNA interference (RNAi) in completely embryonic stem (ES) cell-derived embryos. We show that the gene encoding the RNA-binding factor Grsf1 is important for axial elongation, mid/hindbrain development and axial mesoderm specification, and that Fragilis2, encoding a transmembrane protein, regulates epithelialization of the somites and paraxial mesoderm formation. Intriguingly, the knock-down phenotypes recapitulate several aspects of Wnt pathway mutants, suggesting that these genes are components of the downstream Wnt response. This functional genomic approach allows the rapid identification of functionally important components of embryonic development from large datasets of putative targets.

Key words: Wnt/ß-catenin signaling, Gastrulation, RNA interference (RNAi), Target genes, Expression profiling, Grsf1, Fragilis2, Functional genomics




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
H. Hatano, Y. Kudo, I. Ogawa, T. Tsunematsu, A. Kikuchi, Y. Abiko, and T. Takata
IFN-Induced Transmembrane Protein 1 Promotes Invasion at Early Stage of Head and Neck Cancer Progression
Clin. Cancer Res., October 1, 2008; 14(19): 6097 - 6105.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
U. C. Lange, D. J. Adams, C. Lee, S. Barton, R. Schneider, A. Bradley, and M. A. Surani
Normal Germ Line Establishment in Mice Carrying a Deletion of the Ifitm/Fragilis Gene Family Cluster
Mol. Cell. Biol., August 1, 2008; 28(15): 4688 - 4696.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
C. Ufer, C. C. Wang, M. Fahling, H. Schiebel, B. J. Thiele, E. E. Billett, H. Kuhn, and A. Borchert
Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development
Genes & Dev., July 1, 2008; 22(13): 1838 - 1850.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
W. C. Dunty Jr, K. K. Biris, R. B. Chalamalasetty, M. M. Taketo, M. Lewandoski, and T. P. Yamaguchi
Wnt3a/ -catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation
Development, January 1, 2008; 135(1): 85 - 94.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
M.-L. Dequeant, E. Glynn, K. Gaudenz, M. Wahl, J. Chen, A. Mushegian, and O. Pourquie
A Complex Oscillating Network of Signaling Genes Underlies the Mouse Segmentation Clock
Science, December 8, 2006; 314(5805): 1595 - 1598.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Andreu, S. Colnot, C. Godard, P. Laurent-Puig, D. Lamarque, A. Kahn, C. Perret, and B. Romagnolo
Identification of the IFITM Family as a New Molecular Marker in Human Colorectal Tumors
Cancer Res., February 15, 2006; 66(4): 1949 - 1955.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
S. Bartz and A. L. Jackson
How Will RNAi Facilitate Drug Development?
Sci. Signal., August 2, 2005; 2005(295): pe39 - pe39.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005