PUBLICATION
Overexpression of miR-19b Impairs Cardiac Development in Zebrafish by Targeting ctnnb1
- Authors
- Li, M., Hu, X., Zhu, J., Zhu, C., Zhu, S., Liu, X., Xu, J., Han, S., Yu, Z.
- ID
- ZDB-PUB-140719-2
- Date
- 2014
- Source
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 33: 1988-2002 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental
- Glycogen Synthase Kinase 3/antagonists & inhibitors
- Glycogen Synthase Kinase 3/metabolism
- Heart/embryology
- In Situ Hybridization
- Lithium Chloride/pharmacology
- MicroRNAs/genetics*
- Myocardium/metabolism*
- Myocardium/pathology
- Pericardial Effusion/embryology
- Pericardial Effusion/genetics
- Pericardial Effusion/prevention & control
- Reverse Transcriptase Polymerase Chain Reaction
- Wnt Signaling Pathway/genetics
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- beta Catenin/genetics*
- beta Catenin/metabolism
- PubMed
- 25034767 Full text @ Cell Physiol. Biochem.
Citation
Li, M., Hu, X., Zhu, J., Zhu, C., Zhu, S., Liu, X., Xu, J., Han, S., Yu, Z. (2014) Overexpression of miR-19b Impairs Cardiac Development in Zebrafish by Targeting ctnnb1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 33:1988-2002.
Abstract
Background MicroRNAs are broadly accepted as crucial regulators of cardiovascular development, and dysregulation of their expression has been linked to cardiac disease. MicroRNA cluster miR-17-92 has been implicated in cardiac development and function, yet its defined mechanisms of action in this context are uncertain. Here, we focused on miR-19b, a key component of the miR-17-92 cluster proven to induce cardiomyocyte proliferation in vitro. We aimed to identify the biological significance of miR-19b in cardiac development and its underlying molecular mechanism of action in vivo.
Methods We micro-injected zebrafish embryos with different concentrations (0, 2, 4 and 8 μm) of miR-19b mimics or a negative control, and assessed the embryo malformation rate, mortality rate, hatching rate and heart abnormalities at 72 hours post-fertilization (72 hpf).
Results We found that overexpression of miR-19b impacted left-right symmetry and cardiac development of zebrafish embryos, characterized by pericardial edema, slower heart rate and cardiac looping defects in a dose-dependent manner. Moreover, several important signaling molecules in the Wnt signaling pathway were abnormally expressed, suggesting that overexpression of miR-19b induces the inhibition of the Wnt signaling pathway by directly targeting ctnnb1. Interestingly, the deformed cardiac phenotype was partially rescued by treatment with the GSK3β inhibitor lithium chloride.
Conclusion Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping