PUBLICATION

EpCAM Is an Endoderm-Specific Wnt Derepressor that Licenses Hepatic Development

Authors
Lu, H., Ma, J., Yang, Y., Shi, W., and Luo, L.
ID
ZDB-PUB-130403-19
Date
2013
Source
Developmental Cell   24(5): 543-553 (Journal)
Registered Authors
Luo, Lingfei
Keywords
none
MeSH Terms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Animals
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Real-Time Polymerase Chain Reaction
  • Immunoprecipitation
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Zebrafish
  • RNA, Messenger/genetics
  • In Situ Hybridization
  • Fluorescent Antibody Technique
  • Liver/cytology*
  • Liver/metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6/genetics
  • Low Density Lipoprotein Receptor-Related Protein-6/metabolism*
  • Membrane Glycoproteins/genetics
  • Membrane Glycoproteins/metabolism*
  • Cell Membrane/metabolism
  • Endoderm/physiology*
  • Signal Transduction
  • Animals, Genetically Modified
(all 22)
PubMed
23484855 Full text @ Dev. Cell
Abstract

Mechanisms underlying cell-type-specific response to morphogens or signaling molecules during embryonic development are poorly understood. To learn how response to the liver-inductive Wnt2bb signal is achieved, we identify an endoderm-enriched, single transmembrane protein, epithelial-cell-adhesion-molecule (EpCAM), as an endoderm-specific Wnt derepressor in zebrafish. hi2151/epcam mutants exhibit defective liver development similar to prt/wnt2bb mutants. EpCAM directly binds to Kremen1 and disrupts the Kremen1-Dickkopf2 (Dkk2) interaction, which prevents Kremen1-Dkk2-mediated removal of Lipoprotein-receptor-related protein 6 (Lrp6) from the cell surface. These data lead to a model in which EpCAM derepresses Lrp6 and cooperates with Wnt ligand to activate Wnt signaling through stabilizing membrane Lrp6 and allowing Lrp6 clustering into active signalosomes. Thus, EpCAM cell autonomously licenses and cooperatively activates Wnt2bb signaling in endodermal cells. Our results identify EpCAM as the key molecule and its functional mechanism to confer endodermal cells the competence to respond to the liver-inductive Wnt2bb signal.

Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
as3TgTransgenic Insertion
    hi2151TgTransgenic Insertion
    s854TgTransgenic Insertion
      s870TgTransgenic Insertion
        zf457TgTransgenic Insertion
          1 - 5 of 5
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          dkk2MO1-dkk2MRPHLNO
          epcamMO1-epcamMRPHLNO
          kremen1MO1-kremen1MRPHLNO
          lrp5MO1-lrp5MRPHLNO
          wnt2bbMO1-wnt2bbMRPHLNO
          1 - 5 of 5
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          Fish
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 2 of 2
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          Mapping
          No data available