ArticleAmerican journal of human genetics2001
Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans.
Article in American journal of human genetics, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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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
89 citing papers in PubMed, 365 citations in OpenAlex.
- Cytogenomic Investigation of Individuals with Ovotesticular Difference of Sex Development.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2026Article
- Chromatin-Based Control of Mammalian Sex Determination: Integrating Epigenetic and Metabolic Mechanisms.Advances in experimental medicine and biology · 2026Review
- Building a human pluripotent stem cell-based gonadal niche: improving in vitro systems with in vivo insights.Human reproduction update · 2025Review
- Beyond Gender Binarism: Implications of Sex-Gender Diversity for Health Equity.Healthcare (Basel, Switzerland) · 2025Article
- A novel CUL4B gene variant activating Wnt4/β-catenin signal pathway to karyotype 46, XY female with disorders of sex development.Biological research · 2025Article
- Testicular differentiation in 46,XX DSD: an overview of genetic causes.Frontiers in endocrinology · 2024Review
- Role of Hormones During Gestation and Early Development: Pathways Involved in Developmental Programming.Advances in experimental medicine and biology · 2023Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- Mammalian X-chromosome inactivation: proposed role in suppression of the male programme in genetic females.Journal of genetics · 2022Article
- Becoming female: Ovarian differentiation from an evolutionary perspective.Frontiers in cell and developmental biology · 2022Review
- Full-Length Transcriptome Sequences Provide Insight Into Hermaphroditism of Freshwater Pearl MusselFrontiers in genetics · 2022Article
- Risk-focused differences in molecular processes implicated in SARS-CoV-2 infection: corollaries in DNA methylation and gene expression.Epigenetics & chromatin · 2021Article
- Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing.International journal of molecular sciences · 2021Review
- WNT4 Balances Development vs Disease in Gynecologic Tissues and Women's Health.Endocrinology · 2021Review
- Zebrafish as a Model for Germ Cell Regeneration.Frontiers in cell and developmental biology · 2021Review
- Wnt Pathway: An Integral Hub for Developmental and Oncogenic Signaling Networks.International journal of molecular sciences · 2020Review
- Applying Single-Cell Analysis to Gonadogenesis and DSDs (Disorders/Differences of Sex Development).International journal of molecular sciences · 2020Review
- Identification of male heterogametic sex-determining regions on the Atlantic herring Clupea harengus genome.Journal of fish biology · 2020Article
- Is 'gender disappointment' a unique mental illness?Medicine, health care, and philosophy · 2020Article
- Disorders of Sex Development-Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation.International journal of molecular sciences · 2020Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.
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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.