PUBLICATION

Female Sex Development and Reproductive Duct Formation Depend on Wnt4a in Zebrafish

Authors
Kossack, M.E., High, S.K., Hopton, R.E., Yan, Y.L., Postlethwait, J.H., Draper, B.W.
ID
ZDB-PUB-181118-15
Date
2018
Source
Genetics   211(1): 219-233 (Journal)
Registered Authors
Draper, Bruce, Kossack, Michelle E., Postlethwait, John H., Yan, Yi-Lin
Keywords
reproductive duct, sex determinaion, sex differentiation, wnt4a, zebrafish
MeSH Terms
  • Sex Differentiation*
  • Male
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Female
  • Mullerian Ducts/embryology
  • Mullerian Ducts/metabolism*
  • Fibroblast Growth Factor 9/genetics
  • Fibroblast Growth Factor 9/metabolism
  • Wnt4 Protein/genetics*
  • Wnt4 Protein/metabolism
  • Animals
  • Zebrafish
(all 13)
PubMed
30446521 Full text @ Genetics
Abstract
In laboratory strains of zebrafish, sex determination occurs in the absence of a typical sex chromosome and it is not known what regulates the proportion of animals that develop as males or females. Many sex determination and gonad differentiation genes that act downstream of a sex chromosome are well conserved among vertebrates, but studies that test their contribution to this process have mostly been limited to mammalian models. In mammals, WNT4 is a signaling ligand that is essential for ovary and Müllerian duct development, where it antagonizes the male-promoting FGF9 signal. Wnt4 is well conserved across all vertebrates, but it is not known if Wnt4 plays a role in sex determination and/or the differentiation of sex organs in non-mammalian vertebrates. This question is especially interesting in teleosts, such as zebrafish, because they lack an Fgf9 ortholog. Here we show that wnt4a is the ortholog of mammalian Wnt4, and that wnt4b in teleosts was present in the last common ancestor of humans and zebrafish, but was lost in mammals. We show that wnt4a loss-of-function mutants develop predominantly as males and conclude that wnt4a activity promotes female sex determination and/or differentiation in zebrafish. Additionally, both male and female wnt4a mutants are sterile due to defects in reproductive duct development. Together these results strongly argue that Wnt4a is a conserved regulator of female sex determination and reproductive duct development in mammalian and non-mammalian vertebrates.
Genes / Markers
Figures
Figure Gallery (2 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fh294
    Point Mutation
    fh295
      Point Mutation
      uc44TgTransgenic Insertion
        uc55
          Indel
          uc56
            Indel
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            wnt4CRISPR1-wnt4CRISPR
            1 - 1 of 1
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            Fish
            Antibodies
            Name Type Antigen Genes Isotypes Host Organism
            Ab1-ddx4Rabbit
            1 - 1 of 1
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            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            1 - 1 of 1
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            Mapping
            No data available