ArticlePLoS biology2016
Sexual Fate Change of XX Germ Cells Caused by the Deletion of SMAD4 and STRA8 Independent of Somatic Sex Reprogramming.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- Dynamic blebbing and absence of organelle transfer during mouse oocyte formation.The EMBO journal · 2026Article
- A spatiotemporal transcriptomic atlas of porcine (Sus scrofa) female early gonadal development.Communications biology · 2026Article
- Integrated application of transcriptomics and metabolomics provides insights into gonadal differentiation in Mesocentrotus nudus.Scientific reports · 2025Article
- Single-Cell Transcriptomic Analysis of the Potential Mechanisms of Follicular Development inInternational journal of molecular sciences · 2025Article
- Cell cycle regulation for meiosis in mammalian germ cells.The Journal of reproduction and development · 2023Review
- Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array.Clinical epigenetics · 2022Article
- Functional Modules in Gametogenesis.Frontiers in cell and developmental biology · 2022Article
- SMAD4 Feedback Activates the Canonical TGF-β Family Signaling Pathways.International journal of molecular sciences · 2021Article
- NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells.iScience · 2021Article
- Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice.The EMBO journal · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The differential programming of sperm and eggs in gonads is a fundamental topic in reproductive biology. Although the sexual fate of germ cells is believed to be determined by signaling factors from sexually differentiated somatic cells in fetal gonads, the molecular mechanism that determines germ cell fate is poorly understood. Herein, we show that mothers against decapentaplegic homolog 4 (SMAD4) in germ cells is required for female-type differentiation. Germ cells in Smad4-deficient ovaries respond to retinoic acid signaling but fail to undergo meiotic prophase I, which coincides with the weaker expression of genes required for follicular formation, indicating that SMAD4 signaling is essential for oocyte differentiation and meiotic progression. Intriguingly, germline-specific deletion of Smad4 in Stra8-null female germ cells resulted in the up-regulation of genes required for male gonocyte differentiation, including Nanos2 and PLZF, suggesting the initiation of male-type differentiation in ovaries. Moreover, our transcriptome analyses of mutant ovaries revealed that the sex change phenotype is achieved without global gene expression changes in somatic cells. Our results demonstrate that SMAD4 and STRA8 are essential factors that regulate the female fate of germ cells.
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