PUBLICATION
CCAAT/enhancer-binding protein α is required for hepatic outgrowth via the p53 pathway in zebrafish
- Authors
- Yuan, H., Wen, B., Liu, X., Gao, C., Yang, R., Wang, L., Chen, S., Chen, Z., de The, H., Zhou, J., Zhu, J.
- ID
- ZDB-PUB-151030-9
- Date
- 2015
- Source
- Scientific Reports 5: 15838 (Journal)
- Registered Authors
- Chen, Zhu
- Keywords
- Organogenesis, Zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/physiology
- CCAAT-Enhancer-Binding Proteins/genetics
- CCAAT-Enhancer-Binding Proteins/metabolism*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Hepatocytes/cytology
- Hepatocytes/metabolism
- Liver/embryology*
- Mice
- Signal Transduction/physiology*
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 26511037 Full text @ Sci. Rep.
Citation
Yuan, H., Wen, B., Liu, X., Gao, C., Yang, R., Wang, L., Chen, S., Chen, Z., de The, H., Zhou, J., Zhu, J. (2015) CCAAT/enhancer-binding protein α is required for hepatic outgrowth via the p53 pathway in zebrafish. Scientific Reports. 5:15838.
Abstract
CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping