|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 22 February 2006
doi: 10.1242/dev.02298
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, A-1030
Vienna, Austria.
2 Department of Pharmacology, Graduate School of Medicine, Kyoto University,
Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
3 Max Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10,
13125 Berlin, Germany.
* Author for correspondence (e-mail: hartmann{at}imp.univie.ac.at)
Accepted 24 January 2006
Recently canonical Wnt signaling in the ectoderm has been shown to be required for maintenance of the apical ectodermal ridge (AER) and for dorsoventral signaling. Using conditional gain- and loss-of-function ß-catenin alleles, we have studied the role of mesenchymal ß-catenin activity during limb development. Here, we show that loss of ß-catenin results in limb truncations due to a defect in AER maintenance. Stabilization of ß-catenin also results in truncated limbs, caused by a premature regression of the AER. Concomitantly, in these limbs, the expression of Bmp2, Bmp4 and Bmp7, and of the Bmp target genes Msx1, Msx2 and gremlin, is expanded in the mesenchyme. Furthermore, we found that the expression of Lmx1b, a gene exclusively expressed in the dorsal limb mesenchyme and involved in dorsoventral patterning, is reduced upon loss of ß-catenin activity and is expanded ventrally in gain-of-function limbs. However, the known ectodermal regulators Wnt7a and engrailed 1 are expressed normally. This suggests that Lmx1b is also regulated, in part, by a ß-catenin-mediated Wnt signal, independent of the non-canoncial Wnt7a signaling pathway. In addition, loss of ß-catenin results in a severe agenesis of the scapula. Concurrently, the expression of two genes, Pax1 and Emx2, which have been implicated in scapula development, is lost in ß-catenin loss-of-function limbs; however, only Emx2 is upregulated in gain-of-function limbs. Mesenchymal ß-catenin activity is therefore required for AER maintenance, and for normal expression of Lmx1b and Emx2.
Key words: ß-Catenin, Limb patterning, Scapula, Emx2, AER, Lmx1b, BMP, Dorsoventral axis
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  M. F. Bastida, R. Sheth, and M. A. Ros A BMP-Shh negative-feedback loop restricts Shh expression during limb development Development, November 15, 2009; 136(22): 3779 - 3789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Stepniak, G. L. Radice, and V. Vasioukhin Adhesive and Signaling Functions of Cadherins and Catenins in Vertebrate Development Cold Spring Harb Perspect Biol, November 1, 2009; 1(5): a002949 - a002949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yang Growth and Patterning in the Limb: Signaling Gradients Make the Decision Sci. Signal., January 13, 2009; 2(53): pe3 - pe3. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Grigoryan, P. Wend, A. Klaus, and W. Birchmeier Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of {beta}-catenin in mice Genes & Dev., September 1, 2008; 22(17): 2308 - 2341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. VanKoevering and B. O. Williams Transgenic Mouse Strains for Conditional Gene Deletion During Skeletal Development IBMS BoneKEy, May 1, 2008; 5(5): 151 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yu and D. M. Ornitz FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis Development, February 1, 2008; 135(3): 483 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Day and Y. Yang Wnt and Hedgehog Signaling Pathways in Bone Development J. Bone Joint Surg. Am., February 1, 2008; 90(Supplement_1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Baron and G. Rawadi Targeting the Wnt/{beta}-Catenin Pathway to Regulate Bone Formation in the Adult Skeleton Endocrinology, June 1, 2007; 148(6): 2635 - 2643. [Abstract] [Full Text] [PDF]
|
|
