PUBLICATION

Intrinsic and extrinsic modifiers of the regulative capacity of the developing liver

Authors
Shin, D., Weidinger, G., Moon, R.T., and Stainier, D.Y.
ID
ZDB-PUB-120209-10
Date
2012
Source
Mechanisms of Development   128(11-12): 525-535 (Journal)
Registered Authors
Moon, Randall T., Shin, Donghun, Stainier, Didier, Weidinger, Gilbert
Keywords
sox17, sox32, fgf10a, developmental plasticity, endoderm, zebrafish
MeSH Terms
  • Gene Knockdown Techniques
  • Liver/cytology
  • Liver/embryology*
  • Liver/metabolism
  • Wnt Signaling Pathway/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Wnt Proteins/deficiency
  • Wnt Proteins/genetics
  • Animals, Genetically Modified
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism
  • Fibroblast Growth Factors/physiology*
  • Animals
  • Zebrafish Proteins/genetics
  • SOX Transcription Factors/metabolism*
(all 16)
PubMed
22313811 Full text @ Mech. Dev.
Abstract

Zebrafish wnt2bb mutants initially fail to form a liver, but surprisingly the liver eventually forms in a majority of these embryos which then develop into fertile adults. This unexpected result raised the possibility that identifying the mechanisms of liver formation in wnt2bb mutants could provide insights into the poorly understood yet general principle of regulative development, a process by which some cells can change fate in order to compensate for a deficiency. Here, we identify two factors that underlie the regulative capacity of endodermal tissues: an intrinsic factor, Sox32, a transcription factor of the SoxF subfamily, and an extrinsic factor, Fgf10a. sox32 is expressed in the extrahepatic duct primordium which is not affected in wnt2bb mutants. Blocking Sox32function prevented liver formation in most wnt2bb mutants. fgf10a, which is expressed in the mesenchyme surrounding non-hepatic endodermal cells, negatively impacts the regulative capacity of endodermal tissues. In Wnt/β-catenin signaling deficient embryos, in which the liver completely fails to form, the repression of Fgf10a function allowed liver formation. Altogether, these studies reveal that there is more than one way to form a liver, and provide molecular insights into the phenomenon of tissue plasticity.

Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz15TgTransgenic Insertion
    jh1TgTransgenic Insertion
      m1018TgTransgenic Insertion
        s403
          Point Mutation
          s854TgTransgenic Insertion
            s870TgTransgenic Insertion
              s921TgTransgenic Insertion
                s926TgTransgenic Insertion
                  tbvbo
                    Point Mutation
                    w32TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      fgf5MO1-fgf5MRPHLNO
                      fgf10aMO4-fgf10aMRPHLNO
                      fgf24MO1-fgf24MRPHLNO
                      1 - 3 of 3
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GFPEFGGFP
                      VenusEFGVenus
                      1 - 4 of 4
                      Show
                      Mapping
                      No data available