PUBLICATION

Multiple roles for Med12 in vertebrate endoderm development

Authors
Shin, C.H., Chung, W.S., Hong, S.K., Ober, E.A., Verkade, H., Field, H.A., Huisken, J., and Stainier, D.Y.
ID
ZDB-PUB-080414-12
Date
2008
Source
Developmental Biology   317(2): 467-479 (Journal)
Registered Authors
Chung, Won-Suk, Hong, Sung-Kook, Ober, Elke, Shin, Chong, Stainier, Didier, Verkade, Heather
Keywords
none
MeSH Terms
  • Endoderm/embryology*
  • Endoderm/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • High Mobility Group Proteins/metabolism
  • Gene Expression Regulation, Developmental*
  • In Situ Nick-End Labeling
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • DNA-Binding Proteins/metabolism
  • Mediator Complex
  • SOXF Transcription Factors
  • Base Sequence
  • Sequence Analysis, DNA
  • Cell Line
  • Molecular Sequence Data
  • Polymorphism, Restriction Fragment Length/genetics
  • DNA Primers/genetics
  • Phenotype*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Vertebrates/embryology*
  • Animals
  • Mutagenesis
  • Cell Differentiation/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(all 25)
PubMed
18394596 Full text @ Dev. Biol.
Abstract
In zebrafish, the endoderm originates at the blastula stage from the most marginal blastomeres. Through a series of complex morphogenetic movements and differentiation events, the endodermal germ layer gives rise to the epithelial lining of the digestive tract as well as its associated organs such as the liver, pancreas, and swim bladder. How endodermal cells differentiate into distinct cell types such as hepatocytes or endocrine and exocrine pancreatic cells remains a major question. In a forward genetic screen for genes regulating endodermal organ development, we identified mutations at the shiri locus that cause defects in the development of a number of endodermal organs including the liver and pancreas. Detailed phenotypic analyses indicate that these defects are partially due to a reduction in endodermal expression of the hairy/enhancer of split-related gene, her5, at mid to late gastrulation stages. Using the Tg(0.7her5:EGFP)(ne2067) line, we show that her5 is expressed in the endodermal precursors that populate the pharyngeal region as well as the organ-forming region. We also find that knocking down her5 recapitulates some of the endodermal phenotypes of shiri mutants, further revealing the role of her5 in endoderm development. Positional cloning reveals that shiri encodes Med12, a regulatory subunit of the transcriptional Mediator complex recently associated with two human syndromes. Additional studies indicate that Med12 modulates the ability of Casanova/Sox32 to induce sox17 expression. Thus, detailed phenotypic analyses of embryos defective in a component of the Mediator complex have revealed new insights into discrete aspects of vertebrate endoderm development, and provide possible explanations for the craniofacial and digestive system defects observed in humans with mutations in MED12.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz2TgTransgenic Insertion
    gz4TgTransgenic Insertion
      m1018TgTransgenic Insertion
        ne2067TgTransgenic Insertion
          s432
            Point Mutation
            s435
              Point Mutation
              s854TgTransgenic Insertion
                1 - 7 of 7
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Fish
                Antibodies
                Orthology
                Engineered Foreign Genes
                Marker Marker Type Name
                DsRedEFGDsRed
                EGFPEFGEGFP
                GFPEFGGFP
                1 - 3 of 3
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                Mapping