PUBLICATION

Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates

Authors
Harris, M.P., Rohner, N., Schwarz, H., Perathoner, S., Konstantinidis, P., and Nüsslein-Volhard, C.
ID
ZDB-PUB-081008-12
Date
2008
Source
PLoS Genetics   4(10): e1000206 (Journal)
Registered Authors
Harris, Matthew, Nüsslein-Volhard, Christiane, Rohner, Nicolas
Keywords
Zebrafish, Developmental signaling, Alleles, Epidermis, Teeth, Phenotypes, Skull, Adults
MeSH Terms
  • Ectodysplasins/genetics
  • Ectodysplasins/metabolism*
  • Mutation*
  • Edar Receptor/genetics
  • Edar Receptor/metabolism*
  • Epidermis/growth & development
  • Epidermis/metabolism
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Animals
  • Body Patterning
  • Vertebrates/genetics
  • Vertebrates/growth & development
  • Vertebrates/metabolism
  • Signal Transduction*
  • Humans
  • Skeleton
  • Evolution, Molecular*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Ectodermal Dysplasia/genetics
  • Ectodermal Dysplasia/metabolism*
(all 23)
PubMed
18833299 Full text @ PLoS Genet.
Abstract
The genetic basis of the development and variation of adult form of vertebrates is not well understood. To address this problem, we performed a mutant screen to identify genes essential for the formation of adult skeletal structures of the zebrafish. Here, we describe the phenotypic and molecular characterization of a set of mutants showing loss of adult structures of the dermal skeleton, such as the rays of the fins and the scales, as well as the pharyngeal teeth. The mutations represent adult-viable, loss of function alleles in the ectodysplasin (eda) and ectodysplasin receptor (edar) genes. These genes are frequently mutated in the human hereditary disease hypohidrotic ectodermal dysplasia (HED; OMIM 224900, 305100) that affects the development of integumentary appendages such as hair and teeth. We find mutations in zebrafish edar that affect similar residues as mutated in human cases of HED and show similar phenotypic consequences. eda and edar are not required for early zebrafish development, but are rather specific for the development of adult skeletal and dental structures. We find that the defects of the fins and scales are due to the role of Eda signaling in organizing epidermal cells into discrete signaling centers of the scale epidermal placode and fin fold. Our genetic analysis demonstrates dose-sensitive and organ-specific response to alteration in levels of Eda signaling. In addition, we show substantial buffering of the effect of loss of edar function in different genetic backgrounds, suggesting canalization of this developmental system. We uncover a previously unknown role of Eda signaling in teleosts and show conservation of the developmental mechanisms involved in the formation and variation of both integumentary appendages and limbs. Lastly, our findings point to the utility of adult genetic screens in the zebrafish in identifying essential developmental processes involved in human disease and in morphological evolution.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
dt1248
    Point Mutation
    dt1261
      Point Mutation
      t0621
        Point Mutation
        te370f
          Unknown
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          No data available
          Fish
          Antibodies
          No data available
          Orthology
          Gene Orthology
          eda
          edar
          1 - 2 of 2
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          Engineered Foreign Genes
          No data available
          Mapping
          Entity Type Entity Symbol Location
          Featuredt1261Chr: 5 Details
          Featurete370fChr: 9 Details
          GENEedaChr: 5 Details
          GENEedarChr: 9 Details
          SSLPz1566Chr: 9 Details
          SSLPz10484Chr: 5 Details
          SSLPz13866Chr: 5 Details
          SSLPz20031Chr: 9 Details
          1 - 8 of 8
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