Wnt4 is required for proper male as well as female sexual development.
Genes previously implicated in mammalian sexual development have either a male- or female-specific role. The signaling molecule WNT4 has been shown to be important in female sexual development. Lack of Wnt4 gives rise to masculinization of the XX gonad and we showed previously that the role of WNT4 was to inhibit endothelial and steroidogenic cell migration into the developing ovary. Here we show that Wnt4 also has a function in the male gonad. We find that Sertoli cell differentiation is compromised in Wnt4 mutant testes and that this defect occurs downstream of the testis-determining gene Sry but upstream of Sox9 and Dhh, two early Sertoli cell markers. Genetic analysis shows that this phenotype is primarily due to the action of WNT4 within the early genital ridge. Analysis of different markers identifies the most striking difference in the genital ridge at early stages of its development between wild-type and Wnt4 mutant embryos to be a significant increase of steroidogenic cells in the Wnt4 -/- gonad. These results identify WNT4 as a new factor involved in the mammalian testis determination pathway and show that genes can have a specific but distinct role in both male and female gonad development.
Jeays-Ward
Katherine
K
Section of Gene Function and Regulation, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Dandonneau
Mathieu
M
Swain
Amanda
A
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D005260:Female; D024282:Genes, sry; D006066:Gonads / Q000196:embryology* / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology; D012730:Sex Chromosomes; D012733:Sex Differentiation; D046468:Sexual Development / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D060528:Wnt4 Protein
D015415:Biomarkers; D006609:High Mobility Group Proteins; D011518:Proto-Oncogene Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D002786:Cholesterol Side-Chain Cleavage Enzyme