ArticleDevelopmental biology2012
Testis development requires the repression of Wnt4 by Fgf signaling.
Article in Developmental biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 192 citations in OpenAlex.
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Identification of a Candidate Sex Determination Region and Sex-specific Molecular Markers of Spinibarbus caldwelli.Marine biotechnology (New York, N.Y.) · 2026Article
- Differences of sex development.Nature reviews. Disease primers · 2025Review
- A novel CUL4B gene variant activating Wnt4/β-catenin signal pathway to karyotype 46, XY female with disorders of sex development.Biological research · 2025Article
- Do Sex and Gender Have Separate Identities?Archives of sexual behavior · 2024Review
- Inefficient Sox9 upregulation and absence of Rspo1 repression lead to sex reversal in the B6.XYTIR mouse gonad†.Biology of reproduction · 2024Article
- Testicular differentiation in 46,XX DSD: an overview of genetic causes.Frontiers in endocrinology · 2024Review
- Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review.Frontiers in endocrinology · 2024Review
- FGF-independent MEK1/2 signalling in the developing foetal testis is essential for male germline differentiation in mice.BMC biology · 2023Article
- Single-cell analysis of the developing human ovary defines distinct insights into ovarian somatic and germline progenitors.Developmental cell · 2023Article
- Partial male-to-female reprogramming of mouse fetal testis by Sertoli cell ablation.Development (Cambridge, England) · 2023Article
- From Enrico Sertoli to freemartinism: the many phases of the master testis-determining cell†.Biology of reproduction · 2023Review
- Single-cell transcriptome analysis of male chicken germ cells reveals changes in signaling pathway-related gene expression profiles during mitotic arrest.FEBS open bio · 2023Article
- Biased precursor ingression underlies the center-to-pole pattern of male sex determination in mouse.Development (Cambridge, England) · 2023Article
- FGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination.Clinical genetics · 2023Article
- Article
- Loss of WNT4 in the gubernaculum causes unilateral cryptorchidism and fertility defects.Development (Cambridge, England) · 2022Article
- Using a testis regeneration model, FGF9, LIF, and SCF improve testis cord formation while RA enhances gonocyte survival.Cell and tissue research · 2022Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- Potential antagonistic relationship ofFrontiers in molecular biosciences · 2022Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The bipotential gonad expresses genes associated with both the male and female pathways. Adoption of the male testicular fate is associated with the repression of many female genes including Wnt4. However, the importance of repression of Wnt4 to the establishment of male development was not previously determined. Deletion of either Fgf9 or Fgfr2 in an XY gonad resulted in up-regulation of Wnt4 and male-to-female sex reversal. We investigated whether the deletion if Wnt4 could rescue sex reversal in Fgf9 and Fgfr2 mutants. XY Fgf9/Wnt4 and Fgfr2/Wnt4 double mutants developed testes with male somatic and germ cells present, suggesting that the primary role of Fgf signaling is the repression of female-promoting genes. Thus, the decision to adopt the male fate is based not only on whether male genes, such as Sox9, are expressed, but also on the active repression of female genes, such as Wnt4. Because loss of Wnt4 results in the up-regulation of Fgf9, we also tested the possibility that derepression of Fgf9 was responsible for the aspects of male development observed in XX Wnt4 mutants. However, we found that the relationship between these two signaling factors is not symmetric: loss of Fgf9 in XX Wnt4(-/-) gonads does not rescue their partial female-to-male sex-reversal.
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