PUBLICATION

Planar cell polarity proteins differentially regulate extracellular matrix organization and assembly during zebrafish gastrulation

Authors
Dohn, M.R., Mundell, N.A., Sawyer, L.M., Dunlap, J.A., and Jessen, J.R.
ID
ZDB-PUB-130918-11
Date
2013
Source
Developmental Biology   383(1): 39-51 (Journal)
Registered Authors
Jessen, Jason R.
Keywords
zebrafish, gastrulation, polarity, fibronectin, metalloproteinases, cadherins
MeSH Terms
  • Animals
  • Gastrulation/physiology*
  • Microscopy, Electron, Transmission
  • Microscopy, Confocal
  • Receptors, Cell Surface/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Wnt Signaling Pathway/physiology*
  • Extracellular Matrix/physiology*
  • Immunoprecipitation
  • Cell Polarity/physiology*
  • Glypicans/metabolism
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Blotting, Western
  • Gene Knockdown Techniques
  • Zebrafish/embryology*
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • LIM Domain Proteins/genetics
  • LIM Domain Proteins/metabolism*
(all 21)
PubMed
24021482 Full text @ Dev. Biol.
Abstract

Zebrafish gastrulation cell movements occur in the context of dynamic changes in extracellular matrix (ECM) organization and require the concerted action of planar cell polarity (PCP) proteins that regulate cell elongation and mediolateral alignment. Data obtained using Xenopus laevis gastrulae have shown that integrin–fibronectin interactions underlie the formation of polarized cell protrusions necessary for PCP and have implicated PCP proteins themselves as regulators of ECM. By contrast, the relationship between establishment of PCP and ECM assembly/remodeling during zebrafish gastrulation is unclear. We previously showed that zebrafish embryos carrying a null mutation in the four-pass transmembrane PCP protein vang-like 2 (vangl2) exhibit increased matrix metalloproteinase activity and decreased immunolabeling of fibronectin. These data implicated for the first time a core PCP protein in the regulation of pericellular proteolysis of ECM substrates and raised the question of whether other zebrafish PCP proteins also impact ECM organization. In Drosophila melanogaster, the cytoplasmic PCP protein Prickle binds Van Gogh and regulates its function. Here we report that similar to vangl2, loss of zebrafish prickle1a decreases fibronectin protein levels in gastrula embryos. We further show that Prickle1a physically binds Vangl2 and regulates both the subcellular distribution and total protein level of Vangl2. These data suggest that the ability of Prickle1a to impact fibronectin organization is at least partly due to effects on Vangl2. In contrast to loss of either Vangl2 or Prickle1a function, we find that glypican4 (a Wnt co-receptor) and frizzled7 mutant gastrula embryos with disrupted non-canonical Wnt signaling exhibit the opposite phenotype, namely increased fibronectin assembly. Our data show that glypican4 mutants do not have decreased proteolysis of ECM substrates, but instead have increased cell surface cadherin protein expression and increased intercellular adhesion. These data indicate that Wnt/Glypican4/Frizzled signaling regulates ECM assembly through effects on cadherin-mediated cell cohesion. Together, our results demonstrate that zebrafish Vangl2/Prickle1a and non-canonical Wnt/Frizzled signaling have opposing effects on ECM organization underlying PCP and gastrulation cell movements.

Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
No data available
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
e3
    Point Mutation
    hu3495
      Point Mutation
      m119
        Point Mutation
        m209
          Point Mutation
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          cdh2MO1-cdh2MRPHLNO
          mmp14aMO4-mmp14aMRPHLNO
          mmp14bMO2-mmp14bMRPHLNO
          prickle1aMO1-prickle1aMRPHLNO
          vangl2MO4-vangl2MRPHLNO
          1 - 5 of 5
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          Fish
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab1-mycmonoclonal
            IgG1Mouse
            1 - 1 of 1
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            Orthology
            No data available
            Engineered Foreign Genes
            No data available
            Mapping
            No data available