PUBLICATION

Klf6/copeb is required for hepatic outgrowth in zebrafish and for hepatocyte specification in mouse ES cells

Authors
Zhao, X., Monson, C., Gao, C., Gouon-Evans, V., Matsumoto, N., Sadler, K.C., and Friedman, S.L.
ID
ZDB-PUB-100504-13
Date
2010
Source
Developmental Biology   344(1): 79-93 (Journal)
Registered Authors
Gao, Chuan, Monson, Christopher, Sadler Edepli, Kirsten C.
Keywords
Hepatogenesis, Copeb/klf6, Zebrafish, ES cells, Endoderm
MeSH Terms
  • Hepatocytes/metabolism*
  • Liver/metabolism*
  • Embryonic Stem Cells/cytology*
  • Cell Lineage
  • Mice, Transgenic
  • Cell Proliferation
  • Animals
  • Proto-Oncogene Proteins/physiology*
  • In Situ Hybridization
  • Gene Expression Regulation, Developmental*
  • Models, Biological
  • Mice
  • Cell Differentiation
  • Endoderm/metabolism
  • Zebrafish
  • Kruppel-Like Transcription Factors/physiology*
(all 16)
PubMed
20430021 Full text @ Dev. Biol.
Abstract
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.
Genes / Markers
Figures
Figure Gallery (10 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz15TgTransgenic Insertion
    y1TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      klf6aMO3-klf6aMRPHLNO
      klf6aMO4-klf6aMRPHLNO
      1 - 2 of 2
      Show
      Fish
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRedEFGDsRed
      EGFPEFGEGFP
      1 - 2 of 2
      Show
      Mapping
      No data available