PUBLICATION

Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development

Authors
Le Pabic, P., Ng, C., Schilling, T.F.
ID
ZDB-PUB-141024-1
Date
2014
Source
PLoS Genetics   10: e1004726 (Journal)
Registered Authors
Schilling, Tom
Keywords
Cell polarity, Embryos, Cartilage, Morphogenesis, Chondrocytes, Cell differentiation, Zebrafish, Vertebrates
MeSH Terms
  • Embryonic Development
  • Cadherins/biosynthesis
  • Cadherins/genetics*
  • Gene Expression Regulation, Developmental
  • Morphogenesis/genetics*
  • Zebrafish Proteins/genetics*
  • Cartilage/growth & development*
  • Cell Communication
  • Animals
  • SOX9 Transcription Factor/biosynthesis
  • Cell Polarity/genetics*
  • Humans
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Chondrocytes/metabolism
  • Cell Differentiation/genetics*
(all 16)
PubMed
25340762 Full text @ PLoS Genet.
Abstract
Organogenesis requires coordinated regulation of cellular differentiation and morphogenesis. Cartilage cells in the vertebrate skeleton form polarized stacks, which drive the elongation and shaping of skeletal primordia. Here we show that an atypical cadherin, Fat3, and its partner Dachsous-2 (Dchs2), control polarized cell-cell intercalation of cartilage precursors during craniofacial development. In zebrafish embryos deficient in Fat3 or Dchs2, chondrocytes fail to stack and misregulate expression of sox9a. Similar morphogenetic defects occur in rerea/atr2a-/- mutants, and Fat3 binds REREa, consistent with a model in which Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control differentiation through Sox9. Chimaeric analyses support such a model, and reveal long-range influences of all three factors, consistent with the activation of a secondary signal that regulates polarized cell-cell intercalation. This coordinates the spatial and temporal morphogenesis of chondrocytes to shape skeletal primordia and defects in these processes underlie human skeletal malformations. Similar links between cell polarity and differentiation mechanisms are also likely to control organ formation in other contexts.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ba2TgTransgenic Insertion
    ir1040TgTransgenic Insertion
      tb210
        Point Mutation
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        dchs2MO1-dchs2MRPHLNO
        dchs2MO2-dchs2MRPHLNO
        fat3aMO1-fat3aMRPHLNO
        fat3aMO2-fat3aMRPHLNO
        sox9aMO2-sox9aMRPHLNO
        sox9aMO3-sox9aMRPHLNO
        1 - 6 of 6
        Show
        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-tubg1monoclonal
          IgG1Mouse
          Ab5-tubg1polyclonal
            IgGRabbit
            1 - 2 of 2
            Show
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            TomatoEFGTomato
            1 - 2 of 2
            Show
            Mapping
            No data available