PUBLICATION
Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1
- Authors
- Sadler, K.C., Krahn, K.N., Gaur, N.A., and Ukomadu, C.
- ID
- ZDB-PUB-070210-27
- Date
- 2007
- Source
- Proceedings of the National Academy of Sciences of the United States of America 104(5): 1570-1575 (Journal)
- Registered Authors
- Krahn, Katy Nash, Sadler Edepli, Kirsten C.
- Keywords
- hepatic outgrowth, hepatogenesis, partial hepatectomy
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- CCAAT-Enhancer-Binding Proteins/metabolism
- CCAAT-Enhancer-Binding Proteins/physiology*
- Cell Cycle
- Cell Proliferation
- Cyclin A/physiology
- Cyclin A2
- Gene Expression Regulation, Developmental
- In Situ Hybridization
- Liver/anatomy & histology
- Liver/embryology*
- Liver/metabolism
- Liver/physiology*
- Liver Regeneration*
- Mice
- Mutation
- Time Factors
- Trans-Activators/biosynthesis*
- Trans-Activators/physiology*
- Zebrafish
- Zebrafish Proteins/biosynthesis*
- Zebrafish Proteins/physiology*
- PubMed
- 17242348 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Sadler, K.C., Krahn, K.N., Gaur, N.A., and Ukomadu, C. (2007) Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. Proceedings of the National Academy of Sciences of the United States of America. 104(5):1570-1575.
Abstract
In contrast to the deregulated hepatocellular division that is a feature of many hepatic diseases and malignancies, physiologic liver growth during embryonic development and after partial hepatectomy (PH) in adults is characterized by tightly controlled cell proliferation. We used forward genetic screening in zebrafish to test the hypothesis that a similar genetic program governs physiologic liver growth during hepatogenesis and regeneration after PH. We identified the uhrf1 gene, a cell cycle regulator and transcriptional activator of top2a expression, as required for hepatic outgrowth and embryonic survival. By developing a methodology to perform PH on adult zebrafish, we found that liver regeneration inuhrf1(+/-) adult animals is impaired.uhrf1 transcript levels dramatically increase after PH in both mice, and zebrafish and top2a is not up-regulated in uhrf1(+/-) livers after PH. This indicates that uhrf1 is required for physiologic liver growth in both embryos and adults and illustrates that zebrafish livers regenerate.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping