ArticlePLoS genetics2013
Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 96 citations in OpenAlex.
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- Developmental disorders of the reproductive tract in C57BL/6N-XYThe Journal of veterinary medical science · 2026Article
- Chromatin spatial analysis by METALoci unveils sex-determining 3D regulatory hubs.Nature structural & molecular biology · 2026Article
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- Postnatal Ovarian Transdifferentiation in the Absence of Estrogen Receptor Signaling Is Dependent on Genetic Background.Endocrinology · 2024Article
- Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster.Nature communications · 2024Article
- Extraordinary variability in gene activation and repression programs during gonadal sex differentiation across vertebrates.Frontiers in cell and developmental biology · 2024Article
- Gene expression of male pathway genes sox9 and amh during early sex differentiation in a reptile departs from the classical amniote model.BMC genomics · 2023Article
- Biased precursor ingression underlies the center-to-pole pattern of male sex determination in mouse.Development (Cambridge, England) · 2023Article
- Gonadal Sex Differentiation and Ovarian Organogenesis along the Cortical-Medullary Axis in Mammals.International journal of molecular sciences · 2022Review
- Improved biomarker discovery through a plot twist in transcriptomic data analysis.BMC biology · 2022Article
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- Isolation and Characterization of Germline Stem Cells in Protogynous HermaphroditicInternational journal of molecular sciences · 2022Article
- Becoming female: Ovarian differentiation from an evolutionary perspective.Frontiers in cell and developmental biology · 2022Review
- The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD): I) Physiology, classification, approach, and methodologyII) Biochemical and genetic markers in 46,XX DSD.Advances in laboratory medicine · 2021Review
- Sex determination without sex chromosomes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Review
- Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium.Molecular and cellular endocrinology · 2021Article
- The conserved sex regulator DMRT1 recruits SOX9 in sexual cell fate reprogramming.Nucleic acids research · 2021Article
- The Chromatin State during Gonadal Sex Determination.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2021Review
- Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. To elucidate the first steps of sexual fate specification, we profiled the XX and XY gonad transcriptomes at fine granularity during this period and resolved cascades of gene activation and repression. C57BL/6J (B6) XY gonads showed a consistent ~5-hour delay in the activation of most male pathway genes and repression of female pathway genes relative to 129S1/SvImJ, which likely explains the sensitivity of the B6 strain to male-to-female sex reversal. Using this fine time course data, we predicted novel regulatory genes underlying expression QTLs (eQTLs) mapped in a previous study. To test predictions, we developed an in vitro gonad primary cell assay and optimized a lentivirus-based shRNA delivery method to silence candidate genes and quantify effects on putative targets. We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems.
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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.