ArticleEndocrinology2017
Testis Determination Requires a Specific FGFR2 Isoform to Repress FOXL2.
Article in Endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 68 citations in OpenAlex.
- Characterization of Forkhead Box Transcription Factor (Animals : an open access journal from MDPI · 2026Article
- Sertoli cells as a hub in testicular development and male reproductive.Frontiers in cell and developmental biology · 2025Review
- VEGF-dependent testicular vascularisation involves MEK1/2 signalling and the essential angiogenesis factors, SOX7 and SOX17.BMC biology · 2024Article
- A role for TRPC3 in mammalian testis development.Frontiers in cell and developmental biology · 2024Article
- FGF-independent MEK1/2 signalling in the developing foetal testis is essential for male germline differentiation in mice.BMC biology · 2023Article
- The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.Nature structural & molecular biology · 2023Review
- Partial male-to-female reprogramming of mouse fetal testis by Sertoli cell ablation.Development (Cambridge, England) · 2023Article
- Genetic control of typical and atypical sex development.Nature reviews. Urology · 2023Review
- FGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination.Clinical genetics · 2023Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- CHARGE syndrome-associated proteins FAM172A and CHD7 influence male sex determination and differentiation through transcriptional and alternative splicing mechanisms.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Article
- Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization.Journal of advanced research · 2021Article
- The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation.Scientific reports · 2021Article
- Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9.Cells · 2020Article
- Disorders of Sex Development-Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation.International journal of molecular sciences · 2020Review
- Male Hypogonadism and Disorders of Sex Development.Frontiers in endocrinology · 2020Review
- The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice.PloS one · 2020Article
- Identification of a Goat Intersexuality-Associated Novel Variant Through Genome-Wide Resequencing and Hi-C.Frontiers in genetics · 2020Article
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9 authors at 6 institutions in 2 countries.
Funding
Abstract
Male sex determination in mammals relies on sex determining region Y-mediated upregulation of sex determining region-box 9 (SOX9) expression in XY gonads, whereas Wnt family member (WNT)/R-spondin 1 signaling and forkhead box L2 (FOXL2) drive female sex determination in XX gonads. Fibroblast growth factor (FGF) 9 signaling ensures sustained SOX9 expression through repression of one of the ovarian pathways (WNT signaling), whereas the significance of FGF-mediated repression of the FOXL2 pathway has not been studied. Previously, we demonstrated that FGFR2 is the receptor for FGF9 in the XY gonad. Whether a specific isoform (FGFR2b or FGFR2c) is required was puzzling. Here, we show that FGFR2c is required for male sex determination. Initially, in developing mouse embryos at 12.5 to 13.5 days postcoitum (dpc), XY Fgfr2c-/- gonads appear as ovotestes, with SOX9 and FOXL2 expression predominantly localized to the posterior and anterior gonadal poles, respectively. However, by 15.5 dpc, XY Fgfr2c-/- gonads show complete male-to-female sex reversal, evident by the lack of SOX9 and ectopic expression of FOXL2 throughout the gonads. Furthermore, ablation of the Foxl2 gene leads to partial or complete rescue of gonadal sex reversal in XY Fgfr2c-/- mice. Together with previous findings, our data suggest that testis determination involves FGFR2c-mediated repression of both the WNT4- and FOXL2-driven ovarian-determining pathways.
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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.