PUBLICATION
hnRNP I Inhibits Notch Signaling and Regulates Intestinal Epithelial Homeostasis in the Zebrafish
- Authors
- Yang, J., Chan, C.Y., Jiang, B., Yu, X., Zhu, G.Z., Chen, Y., Barnard, J., and Mei, W.
- ID
- ZDB-PUB-090217-11
- Date
- 2009
- Source
- PLoS Genetics 5(2): e1000363 (Journal)
- Registered Authors
- Mei, Wenyan
- Keywords
- Gastrointestinal tract, Notch signaling, Epithelium, Xenopus, Epithelial cells, Zebrafish, Cell differentiation, Phenotypes
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cells, Cultured
- Heterogeneous-Nuclear Ribonucleoproteins/metabolism*
- Humans
- Intestinal Mucosa/cytology
- Intestinal Mucosa/metabolism*
- Intestines/cytology
- Mice
- Oocytes/metabolism
- Receptors, Notch/antagonists & inhibitors*
- Receptors, Notch/metabolism*
- Signal Transduction*
- Xenopus laevis
- Zebrafish/metabolism
- PubMed
- 19197356 Full text @ PLoS Genet.
Citation
Yang, J., Chan, C.Y., Jiang, B., Yu, X., Zhu, G.Z., Chen, Y., Barnard, J., and Mei, W. (2009) hnRNP I Inhibits Notch Signaling and Regulates Intestinal Epithelial Homeostasis in the Zebrafish. PLoS Genetics. 5(2):e1000363.
Abstract
Regulated intestinal stem cell proliferation and differentiation are required for normal intestinal homeostasis and repair after injury. The Notch signaling pathway plays fundamental roles in the intestinal epithelium. Despite the fact that Notch signaling maintains intestinal stem cells in a proliferative state and promotes absorptive cell differentiation in most species, it remains largely unclear how Notch signaling itself is precisely controlled during intestinal homeostasis. We characterized the intestinal phenotypes of brom bones, a zebrafish mutant carrying a nonsense mutation in hnRNP I. We found that the brom bones mutant displays a number of intestinal defects, including compromised secretory goblet cell differentiation, hyperproliferation, and enhanced apoptosis. These phenotypes are accompanied by a markedly elevated Notch signaling activity in the intestinal epithelium. When overexpressed, hnRNP I destabilizes the Notch intracellular domain (NICD) and inhibits Notch signaling. This activity of hnRNP I is conserved from zebrafish to human. In addition, our biochemistry experiments demonstrate that the effect of hnRNP I on NICD turnover requires the C-terminal portion of the RAM domain of NICD. Our results demonstrate that hnRNP I is an evolutionarily conserved Notch inhibitor and plays an essential role in intestinal homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping