PUBLICATION

Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium

Authors
Matsuda, M., Nogare, D.D., Somers, K., Martin, K., Wang, C., and Chitnis, A.B.
ID
ZDB-PUB-130605-7
Date
2013
Source
Development (Cambridge, England)   140(11): 2387-2397 (Journal)
Registered Authors
Chitnis, Ajay
Keywords
lateral line, Wnt, FGF, Lef1, R-spondin, Dusp6, zebrafish
MeSH Terms
  • Animals
  • Dual Specificity Phosphatase 6/genetics
  • Dual Specificity Phosphatase 6/metabolism*
  • Body Patterning
  • Ligands
  • Green Fluorescent Proteins/metabolism
  • Fibroblast Growth Factor 10/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/physiology*
  • Mutation
  • Lateral Line System/embryology*
  • Cell Proliferation
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
  • Wnt Signaling Pathway
  • Gene Expression Regulation, Developmental*
(all 19)
PubMed
23637337 Full text @ Development
Abstract

The posterior lateral line primordium (PLLp) migrates caudally and periodically deposits neuromasts. Coupled, but mutually inhibitory, Wnt-FGF signaling systems regulate proto-neuromast formation in the PLLp: FGF ligands expressed in response to Wnt signaling activate FGF receptors and initiate proto-neuromast formation. FGF receptor signaling, in turn, inhibits Wnt signaling. However, mechanisms that determine periodic neuromast formation and deposition in the PLLp remain poorly understood. Previous studies showed that neuromasts are deposited closer together and the PLLp terminates prematurely in lef1-deficient zebrafish embryos. It was suggested that this results from reduced proliferation in the leading domain of the PLLp and/or premature incorporation of progenitors into proto-neuromasts. We found that rspo3 knockdown reduces proliferation in a manner similar to that seen in lef1 morphants. However, it does not cause closer neuromast deposition or premature termination of the PLLp, suggesting that such changes in lef1-deficient embryos are not linked to changes in proliferation. Instead, we suggest that they are related to the role of Lef1 in regulating the balance of Wnt and FGF functions in the PLLp. Lef1 determines expression of the FGF signaling inhibitor Dusp6 in leading cells and regulates incorporation of cells into neuromasts; reduction of Dusp6 in leading cells in lef1-deficient embryos allows new proto-neuromasts to form closer to the leading edge. This is associated with progressively slower PLLp migration, reduced spacing between deposited neuromasts and premature termination of the PLLp system.

Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu745
    Point Mutation
    ia4TgTransgenic Insertion
      w26TgTransgenic Insertion
        zf106TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          fgf10aMO1-fgf10aMRPHLNO
          fgf10aMO3-fgf10aMRPHLNO
          lef1MO3-lef1MRPHLNO
          rspo3MO3-rspo3MRPHLNO
          tp53MO4-tp53MRPHLNO
          1 - 5 of 5
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          Fish
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab1-cldnbpolyclonalRabbit
          Ab1-tjp1monoclonalIgG1Mouse
          1 - 2 of 2
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          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