PUBLICATION
Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells
- Authors
- Ueno, S., Weidinger, G., Osugi, T., Kohn, A.D., Golob, J.L., Pabon, L., Reinecke, H., Moon, R.T., and Murry, C.E.
- ID
- ZDB-PUB-070614-9
- Date
- 2007
- Source
- Proceedings of the National Academy of Sciences of the United States of America 104(23): 9685-9690 (Journal)
- Registered Authors
- Moon, Randall T., Weidinger, Gilbert
- Keywords
- heart development, mesoderm, Dickkopf-1, regeneration
- MeSH Terms
-
- Animals
- Cell Differentiation/physiology*
- Embryonic Induction/physiology*
- Embryonic Stem Cells/metabolism*
- Gastrula/embryology
- Heart/embryology*
- Humans
- In Situ Hybridization
- Mice
- Promoter Regions, Genetic/genetics
- Signal Transduction/physiology*
- Wnt Proteins/metabolism*
- Wnt3 Protein
- Wnt3A Protein
- Zebrafish
- beta Catenin/metabolism*
- PubMed
- 17522258 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Ueno, S., Weidinger, G., Osugi, T., Kohn, A.D., Golob, J.L., Pabon, L., Reinecke, H., Moon, R.T., and Murry, C.E. (2007) Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America. 104(23):9685-9690.
Abstract
Understanding pathways controlling cardiac development may offer insights that are useful for stem cell-based cardiac repair. Developmental studies indicate that the Wnt/beta-catenin pathway negatively regulates cardiac differentiation, whereas studies with pluripotent embryonal carcinoma cells suggest that this pathway promotes cardiogenesis. This apparent contradiction led us to hypothesize that Wnt/beta-catenin signaling acts biphasically, either promoting or inhibiting cardiogenesis depending on timing. We used inducible promoters to activate or repress Wnt/beta-catenin signaling in zebrafish embryos at different times of development. We found that Wnt/beta-catenin signaling before gastrulation promotes cardiac differentiation, whereas signaling during gastrulation inhibits heart formation. Early treatment of differentiating mouse embryonic stem (ES) cells with Wnt-3A stimulates mesoderm induction, activates a feedback loop that subsequently represses the Wnt pathway, and increases cardiac differentiation. Conversely, late activation of beta-catenin signaling reduces cardiac differentiation in ES cells. Finally, constitutive overexpression of the beta-catenin-independent ligand Wnt-11 increases cardiogenesis in differentiating mouse ES cells. Thus, Wnt/beta-catenin signaling promotes cardiac differentiation at early developmental stages and inhibits it later. Control of this pathway may promote derivation of cardiomyocytes for basic research and cell therapy applications.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping