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

Kossack, M.E., High, S.K., Hopton, R.E., Yan, Y.L., Postlethwait, J.H., Draper, B.W.
Genetics   211(1): 219-233 (Journal)
Registered Authors
Draper, Bruce, Kossack, Michelle E., Postlethwait, John H., Yan, Yi-Lin
reproductive duct, sex determinaion, sex differentiation, wnt4a, zebrafish
MeSH Terms
  • Animals
  • Female
  • Fibroblast Growth Factor 9/genetics
  • Fibroblast Growth Factor 9/metabolism
  • Male
  • Mullerian Ducts/embryology
  • Mullerian Ducts/metabolism*
  • Sex Differentiation*
  • Wnt4 Protein/genetics*
  • Wnt4 Protein/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
30446521 Full text @ Genetics
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
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes