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

Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/embryology
Zebrafish/embryology*
Zebrafish/genetics
Tumor Suppressor Protein p53/genetics
Tumor Suppressor Protein p53/metabolism*
Mice
Signal Transduction/physiology*
Apoptosis/physiology
Animals
Liver/embryology*
CCAAT-Enhancer-Binding Proteins/genetics
CCAAT-Enhancer-Binding Proteins/metabolism*
Hepatocytes/cytology
Hepatocytes/metabolism

(all 17)

PubMed

26511037 Full text @ Sci. Rep.

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

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
cebpa^rj31/+	standard conditions	Pec-fin	liver cell population proliferation increased occurrence, abnormal	Fig. 4
cebpa^rj31/+	standard conditions	Protruding-mouth	liver fabp1a expression decreased distribution, abnormal	Fig. 5
cebpa^rj31/+	standard conditions	Protruding-mouth	liver fabp1a expression decreased distribution, abnormal	Fig. 2
cebpa^rj31/+	standard conditions	Protruding-mouth	liver apoptotic process increased process quality, abnormal	Fig. 4
cebpa^rj31/+	standard conditions	Protruding-mouth	liver cell population proliferation increased occurrence, abnormal	Fig. 4
cebpa^rj31/+	standard conditions	Protruding-mouth	liver decreased size, abnormal	Fig. 2
cebpa^rj31/+	standard conditions	Protruding-mouth	whole organism bcl2a expression increased amount, abnormal	Fig. 5
cebpa^rj31/+	standard conditions	Protruding-mouth	whole organism bcl2l1 expression increased amount, abnormal	Fig. 5
cebpa^rj31/+	standard conditions	Protruding-mouth	whole organism jun expression increased amount, abnormal	Fig. 5
cebpa^rj31/+	standard conditions	Protruding-mouth	whole organism mycb expression increased amount, abnormal	Fig. 5

1 - 10 of 20

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
rj31		Small Deletion	cebpa
zdf1		Point Mutation	tp53

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cebpa	TALEN1-cebpa	TALEN
tp53	MO7-tp53	MRPHLNO

Fish

Fish
cebpa^rj31/rj31
cebpa^rj31/+
cebpa^rj31/+ + MO7-tp53
tp53^zdf1/zdf1; cebpa^rj31/rj31
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Yuan et al., 2015 ZDB-PUB-151030-9 PMID:26511037

CCAAT/enhancer-binding protein α is required for hepatic outgrowth via the p53 pathway in zebrafish

Yuan et al., 2015

ZDB-PUB-151030-9
PMID:26511037