hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish.
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 prolif...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000363&type=printable |
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| _version_ | 1850107972334649344 |
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| author | Jing Yang Chin Yee Chan Bo Jiang Xueyuan Yu Guo-Zhang Zhu Yiping Chen John Barnard Wenyan Mei |
| author_facet | Jing Yang Chin Yee Chan Bo Jiang Xueyuan Yu Guo-Zhang Zhu Yiping Chen John Barnard Wenyan Mei |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b38123731223480ba0d1c86ccce346c7 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2009-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-b38123731223480ba0d1c86ccce346c72025-08-20T02:38:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-02-0152e100036310.1371/journal.pgen.1000363hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish.Jing YangChin Yee ChanBo JiangXueyuan YuGuo-Zhang ZhuYiping ChenJohn BarnardWenyan MeiRegulated 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000363&type=printable |
| spellingShingle | Jing Yang Chin Yee Chan Bo Jiang Xueyuan Yu Guo-Zhang Zhu Yiping Chen John Barnard Wenyan Mei hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. PLoS Genetics |
| title | hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. |
| title_full | hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. |
| title_fullStr | hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. |
| title_full_unstemmed | hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. |
| title_short | hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. |
| title_sort | hnrnp i inhibits notch signaling and regulates intestinal epithelial homeostasis in the zebrafish |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000363&type=printable |
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