Drs. Andersson and Bryjova contributed equally to this work.
Special Issue Research Article
Genetic interaction between Lrp6 and Wnt5a during mouse development†
Article first published online: 30 SEP 2009
Published 2009 Wiley-Liss, Inc.
Special Issue: Special Issue on WNT Signaling in Development and Disease
Volume 239, Issue 1, pages 237–245, January 2010
How to Cite
Andersson, E. R., Bryjova, L., Biris, K., Yamaguchi, T. P., Arenas, E. and Bryja, V. (2010), Genetic interaction between Lrp6 and Wnt5a during mouse development. Dev. Dyn., 239: 237–245. doi: 10.1002/dvdy.22101
This article is a US government work, and, as such, is in the public domain of the United States of America.
- Issue published online: 15 DEC 2009
- Article first published online: 30 SEP 2009
- Manuscript Accepted: 20 AUG 2009
- Ministry of Education Youth and Sports of the Czech Republic. Grant Number: MSM 0021622430
- Swedish Foundation for Strategic Research (INGVAR and CEDB)
- Swedish Research Council. Grant Number: VR2008:2811 and DBRM
- Norwegian Research Council
- Karolinska Institutet
- Michael J. Fox Foundation
- European Commission (Eurostemcell)
Lrp6 is generally described as a receptor required for signal transduction in the Wnt/β-catenin pathway. Wnt5a, however, is a Wnt ligand that usually does not activate Wnt/β-catenin but rather activates noncanonical Wnt signaling. We have previously shown that Lrp6 can inhibit noncanonical Wnt5a/Wnt11 signaling and that Lrp5/6 loss-of-function produces noncanonical gain-of function defects, which can be rescued by loss of Wnt5a. Here, we describe other phenotypes found in Wnt5a/Lrp6 compound mutant mice, including a worsening of individual Wnt5a or Lrp6 loss of function phenotypes. Lrp6 haploinsufficiency in a Wnt5a−/− background caused spina bifida and exacerbated posterior truncation. Wnt5a−/−Lrp6−/− embryos displayed presomitic mesoderm morphogenesis, somitogenesis, and neurogenesis defects, which are much more severe than in either of the single mutants. Interestingly these results reveal a further level of complexity in processes in which Wnt5a and LRP6 cooperate, or oppose each other, during mouse development. Developmental Dynamics 239:237–245, 2010. Published 2009 Wiley-Liss, Inc.