ArticleDevelopmental biology2013
Disruption of mitotic arrest precedes precocious differentiation and transdifferentiation of pregranulosa cells in the perinatal Wnt4 mutant ovary.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- DMRT1 is required at two steps of ovarian differentiation in rabbits.Science advances · 2026Article
- A single-nucleotide enhancer mutation overrides chromosomal sex to drive XX male development.Nature communications · 2026Article
- Ontogeny of RSPO1, FOXL2, and RUNX1 during ovarian differentiation in the marsupial tammar wallaby.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- A novel CUL4B gene variant activating Wnt4/β-catenin signal pathway to karyotype 46, XY female with disorders of sex development.Biological research · 2025Article
- Postnatal Ovarian Transdifferentiation in the Absence of Estrogen Receptor Signaling Is Dependent on Genetic Background.Endocrinology · 2024Article
- TheScience (New York, N.Y.) · 2023Article
- Becoming female: Ovarian differentiation from an evolutionary perspective.Frontiers in cell and developmental biology · 2022Review
- The role of R-spondin proteins in cancer biology.Oncogene · 2021Review
- 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
- WNT4 Balances Development vs Disease in Gynecologic Tissues and Women's Health.Endocrinology · 2021Review
- Sex Maintenance in Mammals.Genes · 2021Review
- Establishing and maintaining fertility: the importance of cell cycle arrest.Genes & development · 2021Review
- Two distinct pathways of pregranulosa cell differentiation support follicle formation in the mouse ovary.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9.Cells · 2020Article
- Pluripotent Cell Models for Gonadal Research.International journal of molecular sciences · 2019Review
- Dynamics of WNT signaling components in the human ovary from development to adulthood.Histochemistry and cell biology · 2019Article
- Genome-wide identification of FOXL2 binding and characterization of FOXL2 feminizing action in the fetal gonads.Human molecular genetics · 2018Article
- At the Crossroads of Fate-Somatic Cell Lineage Specification in the Fetal Gonad.Endocrine reviews · 2018Review
- ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Mammalian sex determination is controlled by antagonistic pathways that are initially co-expressed in the bipotential gonad and subsequently become male- or female-specific. In XY gonads, testis development is initiated by upregulation of Sox9 by SRY in pre-Sertoli cells. Disruption of either gene leads to complete male-to-female sex reversal. Ovarian development is dependent on canonical Wnt signaling through Wnt4, Rspo1 and β-catenin. However, only a partial female-to-male sex reversal results from disruption of these ovary-promoting genes. In Wnt4 and Rspo1 mutants, there is evidence of pregranulosa cell-to-Sertoli cell transdifferentiation near birth, following a severe decline in germ cells. It is currently unclear why primary sex reversal does not occur at the sex-determining stage, but instead occurs near birth in these mutants. Here we show that Wnt4-null and Rspo1-null pregranulosa cells transition through a differentiated granulosa cell state prior to transdifferentiating towards a Sertoli cell fate. This transition is preceded by a wave of germ cell death that is closely associated with the disruption of pregranulosa cell quiescence. Our results suggest that maintenance of mitotic arrest in pregranulosa cells may preclude upregulation of Sox9 in cases where female sex-determining genes are disrupted. This may explain the lack of complete sex reversal in such mutants at the sex-determining stage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.