Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

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

Authors: Kossack, Michelle E; High, Samantha K; Hopton, Rachel E; Yan, Yi-Lin; Postlethwait, John H; Draper, Bruce W

Published In Genetics, (2019 01)

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 nonmammalian 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 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 nonmammalian vertebrates.

PubMed ID: 30446521 Exiting the NIEHS site

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

Back
to Top