ArticleCell cycle (Georgetown, Tex.)2016
E2f4 and E2f5 are essential for the development of the male reproductive system.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Primary and motile cilia in the efferent ductules: a role for IFT88 in maintaining male fertility.Cellular and molecular life sciences : CMLS · 2026Article
- Male infertility.Systems biology in reproductive medicine · 2025Review
- Role of intraflagellar transport protein IFT140 in the formation and function of motile cilia in mammals.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Novel Core Gene Signature Associated with Inflammation-to-Metaplasia Transition in Influenza A Virus-Infected Lungs.International journal of molecular sciences · 2024Article
- Review
- ARL13B controls male reproductive tract physiology through primary and Motile Cilia.Communications biology · 2024Article
- Endocrine and Transcriptome Changes Associated with Testicular Growth and Differentiation in Atlantic Salmon (Current issues in molecular biology · 2024Article
- RAD51 and Infertility: A Review and Case-Control Study.Biochemical genetics · 2024Review
- Formation and function of multiciliated cells.The Journal of cell biology · 2024Review
- The single-cell chromatin accessibility landscape in mouse perinatal testis development.eLife · 2023Article
- GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program.Cell death & disease · 2023Article
- Decoding the Spermatogenesis Program: New Insights from Transcriptomic Analyses.Annual review of genetics · 2022Review
- E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging.International journal of molecular sciences · 2022Review
- Understanding Retinoblastoma Post-Translational Regulation for the Design of Targeted Cancer Therapies.Cancers · 2022Review
- Review
- Aberrant Gene Expression Profiling in Men With Sertoli Cell-Only Syndrome.Frontiers in immunology · 2022Article
- High Expression of E2F4 Is an Adverse Prognostic Factor and Related to Immune Infiltration in Oral Squamous Cell Carcinoma.BioMed research international · 2022Article
- E2F4's cytoplasmic role in multiciliogenesis is mediated via an N-terminal domain that binds two components of the centriole replication machinery, Deup1 and SAS6.Molecular biology of the cell · 2021Article
- CEP164 is essential for efferent duct multiciliogenesis and male fertility.Reproduction (Cambridge, England) · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The E2F transcription factors are primarily implicated in the regulation of entry and exit from the cell cycle. However, in vivo studies have established additional roles for E2Fs during organ development and homeostasis. With the goal of addressing the intestinal requirements of E2f4 and E2f5, we crossed mice carrying Vil-cre, E2f4 conditional and E2f5 germline alleles. E2f4 deletion had no detectable effect on intestinal development. However, E2f4f/f;E2f5+/-;Vil-cre males, but not E2f4f/f;Vil-cre littermates, were unexpectedly sterile. This defect was not due to defective spermatogenesis. Instead, the seminiferous tubules and rete testes showed significant dilation, and spermatozoa accumulated aberrantly in the rete testis and efferent ducts. Our data show that these problems result from defective efferent ducts, a tissue whose primary function is to concentrate sperm through fluid absorption. First, Vil-cre expression, and consequent E2F4 loss, was specific to the efferent ducts and not other reproductive tract tissues. Second, the E2f4f/f;E2f5+/-;Vil-cre efferent ducts had completely lost multiciliated cells and greatly reduced levels of critical absorptive cell proteins: aquaporin1, a water channel protein, and clusterin, an endocytic marker. Collectively, the observed testis phenotypes suggest a fluid flux defect. Remarkably, we observed rete testis dilation prior to the normal time of seminiferous fluid production, arguing that the efferent duct defects promote excessive secretory activity within the reproductive tract. Finally, we also detect key aspects of these testis defects in E2f5-/- mice. Thus, we conclude that E2f4 and E2f5 display overlapping roles in controlling the normal development of the male reproductive system.
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Registered trials
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