Document Detail

Klf6/copeb is required for hepatic outgrowth in zebrafish and for hepatocyte specification in mouse ES cells.
MedLine Citation:
PMID:  20430021     Owner:  NLM     Status:  MEDLINE    
Krüppel-like factor 6 (Klf6; copeb in zebrafish) is a zinc-finger transcription factor and tumor suppressor gene. Klf6(-)(/)(-) mice have defects in hematopoiesis and angiogenesis and do not form a liver. However, the vascular abnormalities in Klf6(-/-) mice obfuscate its role in liver development since these two processes are linked in mammals. We utilized zebrafish and mouse ES cells to investigate the role of copeb in endoderm specification and hepatogenesis separate from its function in angiogenesis. During zebrafish development, copeb expression is enriched in digestive organs. Morpholino knockdown of copeb blocks expansion of the liver, pancreas and intestine, but does not affect their specification, differentiation or the vascularization of the liver. Decreased hepatocyte proliferation in copeb morphants is accompanied by upregulation of the cell cycle inhibitor, cdkn1a, a Copeb transcriptional target. A cell autonomous role for Klf6 in endoderm and hepatic development was investigated by manipulating Klf6 expression in mouse ES cells driven to differentiate along the hepatic lineage. Expression of the endoderm markers Hnf3beta, Gata4, Sox17, and CxCr4 is not induced in Klf6(-/-) cells but is upregulated in ES cells over-expressing Klf6. Collectively, these findings indicate that copeb/Klf6 is essential for the development of endoderm-derived organs.
Xiao Zhao; Christopher Monson; Chuan Gao; Valerie Gouon-Evans; Nobuyuki Matsumoto; Kirsten C Sadler; Scott L Friedman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  Developmental biology     Volume:  344     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-10     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-93     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Cell Differentiation
Cell Lineage
Cell Proliferation
Embryonic Stem Cells / cytology*
Endoderm / metabolism
Gene Expression Regulation, Developmental*
Hepatocytes / metabolism*
In Situ Hybridization
Kruppel-Like Transcription Factors / physiology*
Liver / metabolism*
Mice, Transgenic
Models, Biological
Proto-Oncogene Proteins / physiology*
Grant Support
K05 AA018408/AA/NIAAA NIH HHS; P20 AA017067/AA/NIAAA NIH HHS; P20 AA017067/AA/NIAAA NIH HHS; P20 AA017067-01/AA/NIAAA NIH HHS; R01 DK037340/DK/NIDDK NIH HHS; R01 DK037340-14/DK/NIDDK NIH HHS; R01 DK056621/DK/NIDDK NIH HHS; R01 DK056621-10/DK/NIDDK NIH HHS; R01 DK080789/DK/NIDDK NIH HHS; R01 DK080789-01A1/DK/NIDDK NIH HHS; R01 DK37340/DK/NIDDK NIH HHS; R01 DK56621/DK/NIDDK NIH HHS; R01DK080789-01A1/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Copeb protein, mouse; 0/Kruppel-Like Transcription Factors; 0/Proto-Oncogene Proteins

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