ArticlePLoS genetics2017
Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 84 citations in OpenAlex.
- Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.Human molecular genetics · 2018Trial
- Strain-Dependent Functional Variation of a Sex Specific Sox9 Enhancer.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Single-nucleus multiomics of murine gonads reveals transcriptional regulatory network underlying supporting lineage differentiation.Science advances · 2026Article
- Upstream SOX9 deletion in a 46,XY girl with acampomelic campomelic dysplasia and absent minipuberty.Orphanet journal of rare diseases · 2025Article
- Complete stranded RNA profiling during early mouse gonad development.NAR molecular medicine · 2025Article
- GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse.Communications biology · 2025Article
- Immediate and late effects of long-term testicular heat stress on the number of seminiferous tubules and cellular content in Santa Inês rams.Animal reproduction · 2025Article
- Gonadal sex reversal at single-cell resolution in Znrf3-deficient mice.Development (Cambridge, England) · 2024Article
- Comparing the roles of sex chromosome-encoded protein homologs in gene regulation.Genes & development · 2024Review
- Two redundant transcription factor binding sites in a single enhancer are essential for mammalian sex determination.Nucleic acids research · 2024Article
- The single-cell chromatin landscape in gonadal cell lineage specification.BMC genomics · 2024Article
- Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review.Frontiers in endocrinology · 2024Review
- Maternal blood transcriptome as a sensor of fetal organ maturation at the end of organogenesis in cattle†.Biology of reproduction · 2023Article
- CDYL reinforces male gonadal sex determination through epigenetically repressingProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural elements promote architectural stripe formation and facilitate ultra-long-range gene regulation at a human disease locus.Molecular cell · 2023Article
- Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.Reproductive biology and endocrinology : RB&E · 2023Article
- In vitro cellular reprogramming to model gonad development and its disorders.Science advances · 2023Article
- Turnover of mammal sex chromosomes in theProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Gadd45g is required for timely Sry expression independently of RSPO1 activity.Reproduction (Cambridge, England) · 2022Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.
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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.