ArticleGenes & development2008
NF1 loss disrupts Schwann cell-axonal interactions: a novel role for semaphorin 4F.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Role of semaphorin 4f in cardiac fibroblasts to regulate matrix production through actin remodeling and YAP/TAZ activation.Apoptosis : an international journal on programmed cell death · 2026Article
- Directional guidance to orient Schwann cell alignment in nerve regeneration requires Plexin-B1.Science advances · 2026Article
- SEMA4F Regulates the Malignant Phenotype of Hepatocellular Carcinoma Cells Through the PI3K-Akt Pathway.Journal of hepatocellular carcinoma · 2026Article
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- Roles of ERK signaling pathway in regulating myelination of the peripheral nervous system.Frontiers in molecular neuroscience · 2025Review
- TheCancers · 2024Review
- A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells.The Journal of biological chemistry · 2023Article
- Basement membrane proteins in extracellular matrix characterize NF1 neurofibroma development and response to MEK inhibitor.The Journal of clinical investigation · 2023Article
- A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells.bioRxiv : the preprint server for biology · 2023Article
- Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.Frontiers in oncology · 2023Article
- Role of nerves in neurofibromatosis type 1-related nervous system tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Semaphorin 3A-Neuropilin-1 Signaling Modulates MMP13 Expression in Human Osteoarthritic Chondrocytes.International journal of molecular sciences · 2022Article
- Neurofibroma Development in Neurofibromatosis Type 1: Insights from Cellular Origin and Schwann Cell Lineage Development.Cancers · 2022Review
- Ras GTPase-activating proteins control neuronal circuit development in barrel cortex layer 4.Frontiers in neuroscience · 2022Article
- Review
- Review
- Why are olfactory ensheathing cell tumors so rare?Cancer cell international · 2019Review
- Polycomb repression regulates Schwann cell proliferation and axon regeneration after nerve injury.Glia · 2018Article
- Current Challenges and Opportunities in Treating Glioblastoma.Pharmacological reviews · 2018Article
- Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST.Frontiers in cellular neuroscience · 2018Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
Neurofibromatosis type 1 (NF1) patients develop neurofibromas, tumors of Schwann cell origin, as a result of loss of the Ras-GAP neurofibromin. In normal nerves, Schwann cells are found tightly associated with axons, while loss of axonal contact is a frequent and important early event in neurofibroma development. However, the molecular basis of this physical interaction or how it is disrupted in cancer remains unclear. Here we show that loss of neurofibromin in Schwann cells is sufficient to disrupt Schwann cell/axonal interactions via up-regulation of the Ras/Raf/ERK signaling pathway. Importantly, we identify down-regulation of semaphorin 4F (Sema4F) as the molecular mechanism responsible for the Ras-mediated loss of interactions. In heterotypic cocultures, Sema4F knockdown induced Schwann cell proliferation by relieving axonal contact-inhibitory signals, providing a mechanism through which loss of axonal contact contributes to tumorigenesis. Importantly, Sema4F levels were strongly reduced in a panel of human neurofibromas, confirming the relevance of these findings to the human disease. This work identifies a novel role for the guidance-molecules semaphorins in the mediation of Schwann cell/axonal interactions, and provides a molecular mechanism by which heterotypic cell-cell contacts control cell proliferation and suppress tumorigenesis. Finally, it provides a new approach for the development of therapies for NF1.
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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.