Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary

Florence Naillat, Wenying Yan, Riikka Karjalainen, Anna Liakhovitskaia, Anatoly Samoylenko, Qi Xu, Zhandong Sun, Bairong Shen, Alexander Medvinsky, Susan Quaggin, Seppo J. Vainio*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The indifferent mammalian embryonic gonad generates an ovary or testis, but the factors involved are still poorly known. The Wnt-4 signal represents one critical female determinant, since its absence leads to partial female-to-male sex reversal in mouse, but its signalling is as well implicated in the testis development. We used the Wnt-4 deficient mouse as a model to identify candidate gonadogenesis genes, and found that the Notum, Phlda2, Runx-1 and Msx1 genes are typical of the wild-type ovary and the Osr2, Dach2, Pitx2 and Tacr3 genes of the testis. Strikingly, the expression of these latter genes becomes reversed in the Wnt-4 knock-out ovary, suggesting a role in ovarian development. We identified the transcription factor Runx-1 as a Wnt-4 signalling target gene, since it is expressed in the ovary and is reduced upon Wnt-4 knock-out. Consistent with this, introduction of the Wnt-4 signal into early ovary cells ex vivo induces Runx-1 expression, while conversely Wnt-4 expression is down-regulated in the absence of Runx-1. We conclude that the Runx-1 gene can be a Wnt-4 signalling target, and that Runx-1 and Wnt-4 are mutually interdependent in their expression. The changes in gene expression due to the absence of Wnt-4 in gonads reflect the sexually dimorphic role of this signal and its complex gene network in mammalian gonad development.

Original languageEnglish (US)
Pages (from-to)163-178
Number of pages16
JournalExperimental Cell Research
Volume332
Issue number2
DOIs
StatePublished - Mar 15 2015

Keywords

  • Female development
  • Germ line
  • Organogenesis
  • Ovary
  • Runx-1
  • Sex determination
  • Somatic cells
  • Testis
  • Wnt-4

ASJC Scopus subject areas

  • Cell Biology

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