ArticleCell death and differentiation2020
SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- A transient epithelial plasticity state defines the developmental window for uterine gland specification.bioRxiv : the preprint server for biology · 2026Article
- Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Retinoic acid antagonizes estrogen signaling to maintain adult uterine cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoding Müllerian Duct Epithelial Regionalization.Molecular reproduction and development · 2025Review
- Cytoplasmatic Localization of Six1 in Male Testis and Spermatogonial Stem Cells.International journal of stem cells · 2024Article
- The histone methyltransferase KMT2D is essential for embryo implantation via regulating precise differentiation of endometrial cells.Cell death discovery · 2024Article
- Single-cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Molecular stratification of the human fetal vaginal epithelium by spatial transcriptome analysis.Acta biochimica et biophysica Sinica · 2024Article
- Combination of computational new approach methodologies for enhancing evidence of biological pathway conservation across species.The Science of the total environment · 2024Article
- Estrogen receptor alpha regulates uterine epithelial lineage specification and homeostasis.iScience · 2023Article
- Bone morphogenetic protein signaling is a possible therapeutic target in gynecologic cancer.Cancer science · 2023Review
- EctomesenchymalFrontiers in genetics · 2023Article
- Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues.Nature cell biology · 2022Article
- Mechanistic Drivers of Müllerian Duct Development and Differentiation Into the Oviduct.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
During female mammal reproductive tract development, epithelial cells of the lower Müllerian duct are committed to become stratified squamous epithelium of the vagina and ectocervix, when the expression of ΔNp63 transcription factor is induced by mesenchymal cells. The absence of ΔNp63 expression leads to adenosis, the putative precursor of vaginal adenocarcinoma. Our previous studies with genetically engineered mouse models have established that fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP)/SMAD, and activin A/runt-related transcription factor 1 (RUNX1) signaling pathways are independently required for ΔNp63 expression in Müllerian duct epithelium (MDE). Here, we report that sine oculis homeobox homolog 1 (SIX1) plays a critical role in the activation of ΔNp63 locus in MDE as a downstream transcription factor of mesenchymal signals. In the developing mouse reproductive tract, SIX1 expression was restricted to MDE within the future cervix and vagina. SIX1 expression was totally absent in SMAD4 null MDE and was reduced in RUNX1 null and FGFR2 null MDE, indicating that SIX1 is under the control of vaginal mesenchymal factors: BMP4, activin A and FGF7/10. Furthermore, Six1, Runx1, and Smad4 gene-dose-dependently activated ΔNp63 expression in MDE within the vaginal fornix. Using a mouse model of diethylstilbestrol (DES)-associated vaginal adenosis, we found DES action through epithelial estrogen receptor α (ESR1) inhibits activation of ΔNp63 locus in MDE by transcriptionally repressing SIX1 and RUNX1 in the vaginal fornix.
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Identifiers
32572167PMC7852590W3035997443What OpenQuestion holds
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.