ArticlePloS one2013
Aristaless related homeobox gene, Arx, is implicated in mouse fetal Leydig cell differentiation possibly through expressing in the progenitor cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 84 citations in OpenAlex.
- Spatiotemporally primed coelomic epithelium and supporting-like cells establish the dual origin of granulosa cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Functional and transcriptomic insights into 46,XY disorders of sex development associated with NR5A1 gene variants.Biology of sex differences · 2026Article
- Specification of the interstitial cell lineage in the fetal mouse ovary requires balanced Notch signaling.bioRxiv : the preprint server for biology · 2026Article
- Evidence of Sertoli cell lineage contribution to the rete testis population during embryonic development.Frontiers in cell and developmental biology · 2026Article
- Ovarian development is driven by early spatiotemporal priming of the coelomic epithelium.bioRxiv : the preprint server for biology · 2025Article
- Generation of a Nr2f2-driven inducible Cre mouse to target interstitial cells in the reproductive system†.Biology of reproduction · 2025Article
- Article
- NR2F2 regulation of interstitial cell fate in the embryonic mouse testis and its impact on differences of sex development.Nature communications · 2025Article
- Sertoli cells as a hub in testicular development and male reproductive.Frontiers in cell and developmental biology · 2025Review
- Fetal Leydig cells: What we know and what we don't.Molecular reproduction and development · 2024Review
- Direct male development in chromosomally ZZ zebrafish.Frontiers in cell and developmental biology · 2024Article
- TheScience (New York, N.Y.) · 2023Article
- Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway.Communications biology · 2022Article
- Behavior and Functional Roles of CD34International journal of molecular sciences · 2022Review
- Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad.Science advances · 2022Article
- The Fate of Leydig Cells in Men with Spermatogenic Failure.Life (Basel, Switzerland) · 2022Review
- Identification of Rat Testicular Leydig Precursor Cells by Single-Cell-RNA-Sequence Analysis.Frontiers in cell and developmental biology · 2022Article
- The expression of aristaless-related homeobox in neural progenitors of gyrencephalic carnivore ferrets.Biochemistry and biophysics reports · 2021Article
- Leydig Cell and Spermatogenesis.Advances in experimental medicine and biology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of the testis begins with the expression of the SRY gene in pre-Sertoli cells. Soon after, testis cords containing Sertoli and germ cells are formed and fetal Leydig cells subsequently develop in the interstitial space. Studies using knockout mice have indicated that multiple genes encoding growth factors and transcription factors are implicated in fetal Leydig cell differentiation. Previously, we demonstrated that the Arx gene is implicated in this process. However, how ARX regulates Leydig cell differentiation remained unknown. In this study, we examined Arx KO testes and revealed that fetal Leydig cell numbers largely decrease throughout the fetal life. Since our study shows that fetal Leydig cells rarely proliferate, this decrease in the KO testes is thought to be due to defects of fetal Leydig progenitor cells. In sexually indifferent fetal gonads of wild type, ARX was expressed in the coelomic epithelial cells and cells underneath the epithelium as well as cells at the gonad-mesonephros border, both of which have been described to contain progenitors of fetal Leydig cells. After testis differentiation, ARX was expressed in a large population of the interstitial cells but not in fetal Leydig cells, raising the possibility that ARX-positive cells contain fetal Leydig progenitor cells. When examining marker gene expression, we observed cells as if they were differentiating into fetal Leydig cells from the progenitor cells. Based on these results, we propose that ARX acts as a positive factor for differentiation of fetal Leydig cells through functioning at the progenitor stage.
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