ArticleDevelopmental biology2013
Constitutive activation of NOTCH1 signaling in Sertoli cells causes gonocyte exit from quiescence.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
- Comparison of Sertoli cells in duck testes pre- and post-sexual maturation.Poultry science · 2026Article
- Spermatogonial stem cell markers and distribution in different regions of the testis of adult Nile tilapia (Animal reproduction · 2026Article
- Article
- Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis.Stem cell research & therapy · 2024Review
- Comparative Transcriptome Analysis Reveals Sexually Dimorphic Gene Expression in the Gonads ofAnimals : an open access journal from MDPI · 2023Article
- Notch pathway is required for protection against heat stress in spermatogonial stem cells in medaka.Fish physiology and biochemistry · 2023Article
- Article
- Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions.Frontiers in endocrinology · 2023Review
- Article
- Effects of postnatal exposure to tetrabromobisphenol A on testis development in mice and early key events.Archives of toxicology · 2022Article
- Dysregulation of Notch-FGF signaling axis in germ cells results in cystic dilation of the rete testis in mice.Journal of cell communication and signaling · 2022Article
- Assessment of Zearalenone-Induced Cell Survival and of Global Gene Regulation in Mouse TM4 Sertoli Cells.Toxins · 2022Article
- Functional Importance of Mini-Puberty in Spermatogenic Stem Cell Formation.Frontiers in cell and developmental biology · 2022Review
- Sertoli Cell-Germ Cell Interactions Within the Niche: Paracrine and Juxtacrine Molecular Communications.Frontiers in endocrinology · 2022Review
- Cell-fate transition and determination analysis of mouse male germ cells throughout development.Nature communications · 2021Article
- Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice.International journal of molecular sciences · 2021Article
- Involvement of Cytokines and Hormones in the Development of Spermatogenesis In Vitro from Spermatogonial Cells of Cyclophosphamide-Treated Immature Mice.International journal of molecular sciences · 2021Article
- Transcriptome Sequencing and Comparative Analysis of Amphoteric ESCs and PGCs in Chicken (Animals : an open access journal from MDPI · 2020Article
- Crosstalk between Androgen-ZIP9 Signaling and Notch Pathway in Rodent Sertoli Cells.International journal of molecular sciences · 2020Article
- Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Notch signaling components have long been detected in Sertoli and germ cells in the developing and mature testis. However, the role of this pathway in testis development and spermatogenesis remains unknown. Using reporter mice expressing green fluorescent protein following Notch receptor activation, we found that Notch signaling was active in Sertoli cells at various fetal, neonatal, and adult stages. Since Notch signaling specifies stem cell fate in many developing and mature organ systems, we hypothesized that maintenance and differentiation of gonocytes and/or spermatogonial stem cells would be modulated through this pathway in Sertoli cells. To this end, we generated mutant mice constitutively expressing the active, intracellular domain of NOTCH1 (NICD1) in Sertoli cells. We found that mutant Sertoli cells were morphologically normal before and after birth, but presented a number of functional changes that drastically affected gonocyte numbers and physiology. We observed aberrant exit of gonocytes from mitotic arrest, migration toward cord periphery, and premature differentiation before birth. These events, presumably unsupported by the cellular microenvironment, were followed by gonocyte apoptosis and near complete disappearance of the gonocytes by day 2 after birth. Molecular analysis demonstrated that these effects are correlated with a dysregulation of Sertoli-expressed genes that are required for germ cell maintenance, such as Cyp26b1 and Gdnf. Taken together, our results demonstrate that Notch signaling is active in Sertoli cells throughout development and that proper regulation of Notch signaling in Sertoli cells is required for the maintenance of gonocytes in an undifferentiated state during fetal development.
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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.