ArticleEndocrinology2014
ROS1 signaling regulates epithelial differentiation in the epididymis.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Clustering and a conformational switch drive activation of the mammalian receptor tyrosine kinase ROS1.Nature communications · 2026Article
- Age-dependent immune responses and resident cell dynamics in young mice following pneumonia.iScience · 2026Article
- Postnatal development of the epididymis from birth until puberty of indigenous sheep (Barind-type) in Bangladesh.Journal of advanced veterinary and animal research · 2025Article
- Inhibition of ROS1 activity with lorlatinib reversibly suppresses fertility in male mice.Andrology · 2025Article
- Gonadotoxicity of immunotherapy and targeted agents in patients with cancer and impact on subsequent pregnancies.Human reproduction (Oxford, England) · 2025Review
- Maternal protein restriction affects the differentiation of cells in the epididymal epithelium lining of 44-day-old rats.Biology open · 2025Article
- Identification and expression profile analysis of circRNAs associated with goat uterus with different fecundity during estrous cycle.BMC genomics · 2025Article
- Staining patterns of PNA and UEA-I lectins in the postnatal developing male genital excurrent duct epithelium in mice.Journal of advanced veterinary and animal research · 2024Article
- RUNX transcription factors are essential in maintaining epididymal epithelial differentiation.Cellular and molecular life sciences : CMLS · 2024Article
- Distinct actions of testicular endocrine and lumicrine signaling on the proximal epididymal transcriptome.Reproductive biology and endocrinology : RB&E · 2024Article
- Expression of NELL2/NICOL-ROS1 lumicrine signaling-related molecules in the human male reproductive tract.Reproductive biology and endocrinology : RB&E · 2024Article
- LIMS-Kinase provides sensitive and generalizable label-freeCell reports. Physical science · 2023Article
- Adhesion G protein-coupled receptor G2 is dispensable for lumicrine signaling regulating epididymal initial segment differentiation and gene expression†.Biology of reproduction · 2023Article
- Epithelial and mesenchymal fate decisions in Wolffian duct development.Trends in endocrinology and metabolism: TEM · 2023Review
- A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility.Nature communications · 2023Article
- Hedgehog signaling regulates Wolffian duct development through the primary cilium†.Biology of reproduction · 2023Article
- ROS1-dependent cancers - biology, diagnostics and therapeutics.Nature reviews. Clinical oncology · 2021Review
- A framework for high-resolution phenotyping of candidate male infertility mutants: from human to mouse.Human genetics · 2021Review
- The expression and localization of V-ATPase and cytokeratin 5 during postnatal development of the pig epididymis.Asian-Australasian journal of animal sciences · 2020Article
- NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility.Science (New York, N.Y.) · 2020Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
Abstract
The initial segment (IS) of the epididymis plays an essential role in male fertility. The IS epithelium is undifferentiated and nonfunctional at birth. Prior to puberty, the epithelium undergoes differentiation that leads to the formation of a fully functional organ. However, the mechanistic details of this program are not well understood. To explore this further, we used genetic engineering to create a kinase dead allele of the ROS1 receptor tyrosine kinase in mice and studied the effects of ROS1 tyrosine kinase activity on the differentiation of the IS epithelium. We show that the expression and activation of ROS1 coincides with the onset of differentiation and is exclusively located in the IS of the maturing and adult mouse epididymides. Here we demonstrate that the differentiation of the IS is dependent on the kinase activity of ROS1 and its downstream effector MEK1/2-ERK1/2 signaling axis. Using genetic engineering, we show that germ line ablation of ROS1 kinase activity leads to a failure of the IS epithelium to differentiate, and as a consequence sperm maturation and infertility were dramatically perturbed. Pharmacological inhibition of ROS1 kinase activity in the developing epididymis, however, only delayed differentiation transiently and did not result in infertility. Our results demonstrate that ROS1 kinase activity and the ensuing MEK1/2-ERK1/2 signaling are necessary for the postnatal development of the IS epithelium and that a sustained ablation of ROS1 kinase activity within the critical window of terminal differentiation abrogate the function of the epididymis and leads to sterility.
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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.