PUBLICATION

fras1 shapes endodermal pouch 1 and stabilizes zebrafish pharyngeal skeletal development

Authors
Talbot, J.C., Walker, M.B., Carney, T.J., Huycke, T.R., Yan, Y.L., Bremiller, R.A., Gai, L., Delaurier, A., Postlethwait, J.H., Hammerschmidt, M., and Kimmel, C.B.
ID
ZDB-PUB-120718-19
Date
2012
Source
Development (Cambridge, England)   139(15): 2804-2813 (Journal)
Registered Authors
Carney, Tom, DeLaurier, April, Hammerschmidt, Matthias, Huycke, Tyler, Kimmel, Charles B., Postlethwait, John H., Talbot, Jared, Walker, Macie B., Yan, Yi-Lin
Keywords
fras1, zebrafish, craniofacial, Fraser syndrome, developmental instability
MeSH Terms
  • Skeleton
  • Zebrafish
  • Fraser Syndrome/genetics
  • Animals
  • Humans
  • Models, Biological
  • Bone and Bones/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • Crosses, Genetic
  • Mutation
  • Models, Genetic
  • In Situ Hybridization
  • Cartilage/cytology
  • Cartilage/metabolism
  • Endoderm/metabolism
  • Gene Expression Regulation, Developmental*
  • Extracellular Matrix Proteins/genetics*
  • Extracellular Matrix Proteins/physiology*
(all 19)
PubMed
22782724 Full text @ Development
Abstract

Lesions in the epithelially expressed human gene FRAS1 cause Fraser syndrome, a complex disease with variable symptoms, including facial deformities and conductive hearing loss. The developmental basis of facial defects in Fraser syndrome has not been elucidated. Here we show that zebrafish fras1 mutants exhibit defects in facial epithelia and facial skeleton. Specifically, fras1 mutants fail to generate a late-forming portion of pharyngeal pouch 1 (termed late-p1) and skeletal elements adjacent to late-p1 are disrupted. Transplantation studies indicate that fras1 acts in endoderm to ensure normal morphology of both skeleton and endoderm, consistent with well-established epithelial expression of fras1. Late-p1 formation is concurrent with facial skeletal morphogenesis, and some skeletal defects in fras1 mutants arise during late-p1 morphogenesis, indicating a temporal connection between late-p1 and skeletal morphogenesis. Furthermore, fras1 mutants often show prominent second arch skeletal fusions through space occupied by late-p1 in wild type. Whereas every fras1 mutant shows defects in late-p1 formation, skeletal defects are less penetrant and often vary in severity, even between the left and right sides of the same individual. We interpret the fluctuating asymmetry in fras1 mutant skeleton and the changes in fras1 mutant skeletal defects through time as indicators that skeletal formation is destabilized. We propose a model wherein fras1 prompts late-p1 formation and thereby stabilizes skeletal formation during zebrafish facial development. Similar mechanisms of stochastic developmental instability might also account for the high phenotypic variation observed in human FRAS1 patients.

Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1048
    Point Mutation
    b1130
      Point Mutation
      ne1911TgTransgenic Insertion
        te262d
          Point Mutation
          tm95b
            Point Mutation
            vu234TgTransgenic Insertion
              zc81TgTransgenic Insertion
              1 - 7 of 7
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab1-fras1polyclonalRabbit
              Ab1-tp63monoclonalIgG2aMouse
              1 - 2 of 2
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              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              mRFPEFGmRFP
              RFPEFGRFP
              1 - 3 of 3
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              Mapping
              No data available