PUBLICATION
The Wnt/beta-catenin pathway regulates cardiac valve formation
- Authors
- Hurlstone, A.F., Haramis, A.P., Wienholds, E., Begthel, H., Korving, J., van Eeden, F., Cuppen, E., Zivkovic, D., Plasterk, R.H., and Clevers, H.
- ID
- ZDB-PUB-031014-8
- Date
- 2003
- Source
- Nature 425(6958): 633-637 (Journal)
- Registered Authors
- Clevers, Hans, Cuppen, Edwin, Haramis, Anna-Pavlina, Jongejan-Zivkovic, Dana, Plasterk, Ronald H.A., van Eeden, Freek, Wienholds, Erno
- Keywords
- none
- MeSH Terms
-
- Adenomatous Polyposis Coli Protein/genetics
- Adenomatous Polyposis Coli Protein/metabolism
- Animals
- Cell Division
- Cell Lineage
- Cytoskeletal Proteins/genetics
- Cytoskeletal Proteins/metabolism*
- Gene Expression Regulation, Developmental
- Genes, APC
- Genotype
- Heart Valves/abnormalities
- Heart Valves/cytology
- Heart Valves/embryology*
- Heart Valves/metabolism
- Humans
- Intercellular Signaling Peptides and Proteins
- Mutation/genetics
- Proteins/genetics
- Proteins/metabolism
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins/metabolism*
- Signal Transduction
- Trans-Activators/genetics
- Trans-Activators/metabolism*
- Wnt Proteins
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- beta Catenin
- PubMed
- 14534590 Full text @ Nature
Citation
Hurlstone, A.F., Haramis, A.P., Wienholds, E., Begthel, H., Korving, J., van Eeden, F., Cuppen, E., Zivkovic, D., Plasterk, R.H., and Clevers, H. (2003) The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature. 425(6958):633-637.
Abstract
Truncation of the tumour suppressor adenomatous polyposis coli (Apc) constitutively activates the Wnt/beta-catenin signalling pathway. Apc has a role in development: for example, embryos of mice with truncated Apc do not complete gastrulation. To understand this role more fully, we examined the effect of truncated Apc on zebrafish development. Here we show that, in contrast to mice, zebrafish do complete gastrulation. However, mutant hearts fail to loop and form excessive endocardial cushions. Conversely, overexpression of Apc or Dickkopf 1 (Dkk1), a secreted Wnt inhibitor, blocks cushion formation. In wild-type hearts, nuclear beta-catenin, the hallmark of activated canonical Wnt signalling, accumulates only in valve-forming cells, where it can activate a Tcf reporter. In mutant hearts, all cells display nuclear beta-catenin and Tcf reporter activity, while valve markers are markedly upregulated. Concomitantly, proliferation and epithelial-mesenchymal transition, normally restricted to endocardial cushions, occur throughout the endocardium. Our findings identify a novel role for Wnt/beta-catenin signalling in determining endocardial cell fate.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping