PUBLICATION

Wnt/Dkk Negative Feedback Regulates Sensory Organ Size in Zebrafish

Authors
Wada, H., Ghysen, A., Asakawa, K., Abe, G., Ishitani, T., and Kawakami, K.
ID
ZDB-PUB-130816-2
Date
2013
Source
Current biology : CB   23(16): 1559-65 (Journal)
Registered Authors
Ghysen, Alain, Ishitani, Tohru, Kawakami, Koichi, Wada, Hironori
Keywords
none
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/physiology*
  • Wnt Signaling Pathway*
  • Cell Differentiation
  • Regeneration
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/physiology
  • Feedback
  • Polymerase Chain Reaction
  • Gene Expression Regulation, Developmental
  • Lateral Line System/anatomy & histology
  • Lateral Line System/growth & development*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Intercellular Signaling Peptides and Proteins/genetics*
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Cell Proliferation
  • Organ Size
  • Animals
(all 21)
PubMed
23891113 Full text @ Curr. Biol.
Abstract

Correct organ size must involve a balance between promotion and inhibition of cell proliferation. A mathematical model has been proposed in which an organ is assumed to produce its own growth activator as well as a growth inhibitor, but there is as yet no molecular evidence to support this model. The mechanosensory organs of the fish lateral line system (neuromasts) are composed of a core of sensory hair cells surrounded by nonsensory support cells. Sensory cells are constantly replaced and are regenerated from surrounding nonsensory cells, while each organ retains the same size throughout life. Moreover, neuromasts also bud off new neuromasts, which stop growing when they reach the same size. Here, we show that the size of neuromasts is controlled by a balance between growth-promoting Wnt signaling activity in proliferation-competent cells and Wnt-inhibiting Dkk activity produced by differentiated sensory cells. This negative feedback loop from Dkk (secreted by differentiated cells) on Wnt-dependent cell proliferation (in surrounding cells) also acts during regeneration to achieve size constancy. This study establishes Wnt/Dkk as a novel mechanism to determine the final size of an organ.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu745
    Point Mutation
    kyu1TgTransgenic Insertion
      nk73aGtTransgenic Insertion
        nkuasgfp1aTgTransgenic Insertion
          nns8TgTransgenic Insertion
            zf106TgTransgenic Insertion
              zf422TgTransgenic Insertion
                zf423TgTransgenic Insertion
                  zf424TgTransgenic Insertion
                    zf425TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      dkk1aMO1-dkk1aMRPHLNO
                      dkk1bMO5-dkk1bMRPHLNO
                      dkk2MO2-dkk2MRPHLNO
                      kremen1MO4-kremen1MRPHLNO
                      lef1MO3-lef1MRPHLNO
                      1 - 5 of 5
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                      Fish
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      d2EGFPEFGd2EGFP
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GAL4FFEFGGAL4FF
                      RFPEFGRFP
                      TomatoEFGTomato
                      1 - 6 of 6
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                      Mapping
                      No data available