ArticlePloS one2011
Human RSPO1/R-spondin1 is expressed during early ovary development and augments β-catenin signaling.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Identification of six new susceptibility loci for invasive epithelial ovarian cancer.Nature genetics · 2015Pooled it
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- Beyond Gender Binarism: Implications of Sex-Gender Diversity for Health Equity.Healthcare (Basel, Switzerland) · 2025Article
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- Female-Biased Expression ofAnimals : an open access journal from MDPI · 2023Article
- Loss of LGR4/GPR48 causes severe neonatal salt wasting due to disrupted WNT signaling altering adrenal zonation.The Journal of clinical investigation · 2023Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- Potential antagonistic relationship ofFrontiers in molecular biosciences · 2022Article
- Becoming female: Ovarian differentiation from an evolutionary perspective.Frontiers in cell and developmental biology · 2022Review
- Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models.Frontiers in cell and developmental biology · 2022Review
- Plant Occurring Flavonoids as Modulators of the Aryl Hydrocarbon Receptor.Molecules (Basel, Switzerland) · 2021Review
- Advances in Female Germ Cell Induction from Pluripotent Stem Cells.Stem cells international · 2021Review
- Research Advances in Gametogenesis and Embryogenesis Using Pluripotent Stem Cells.Frontiers in cell and developmental biology · 2021Review
- Ligand-Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development.Frontiers in cell and developmental biology · 2021Article
- 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
- Diagnosis and Management of Inherited Palmoplantar Keratodermas.Acta dermato-venereologica · 2020Review
- Molecular Characterization of XX Maleness.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Human testis development starts from around 42 days post conception with a transient wave of SRY expression followed by up-regulation of testis specific genes and a distinct set of morphological, paracrine and endocrine events. Although anatomical changes in the ovary are less marked, a distinct sub-set of ovary specific genes are also expressed during this time. The furin-domain containing peptide R-spondin1 (RSPO1) has recently emerged as an important regulator of ovary development through up-regulation of the WNT/β-catenin pathway to oppose testis formation. Here, we show that RSPO1 is upregulated in the ovary but not in the testis during critical early stages of gonad development in humans (between 6-9 weeks post conception), whereas the expression of the related genes WNT4 and CTNNB1 (encoding β catenin) is not significantly different between these tissues. Furthermore, reduced R-spondin1 function in the ovotestis of an individual (46,XX) with a RSPO1 mutation leads to reduced β-catenin protein and WNT4 mRNA levels, consistent with down regulation of ovarian pathways. Transfection of wild-type RSPO1 cDNA resulted in weak dose-dependent activation of a β-catenin responsive TOPFLASH reporter (1.8 fold maximum), whereas co-transfection of CTNNB1 (encoding β-catenin) with RSPO1 resulted in dose-dependent synergistic augmentation of this reporter (approximately 10 fold). Furthermore, R-spondin1 showed strong nuclear localization in several different cell lines. Taken together, these data show that R-spondin1 is upregulated during critical stages of early human ovary development and may function as a tissue-specific amplifier of β-catenin signaling to oppose testis determination.
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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.