ArticleBrain and behavior2021
Prenatal overexpression of platelet-derived growth factor receptor A results in central nervous system hypomyelination.
Article in Brain and behavior, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Transcriptional Heterogeneity of Oligodendrocytes: Molecular Basis of Diversity Across Development, Brain Regions, and Neurological Diseases.Neurology international · 2026Review
- Oligodendrocyte Egr2 Mediates the Beneficial Effect of Resocialization on the Social Ability of Socially Isolated Mice.Neuroscience bulletin · 2026Article
- N-Acetylglucosamine Selectively Attenuates Neuroinflammation in a Mouse Model of Mitochondrial Dysfunction.Acta physiologica (Oxford, England) · 2026Article
- PDGFRα is required for postnatal cerebral perivascular fibroblast development.Developmental biology · 2026Article
- Modeling glioma intratumoral heterogeneity with primary human neural stem and progenitor cells.Stem cell reports · 2025Article
- PAK1 regulates oligodendroglial proliferation and repopulation in homeostatic and demyelinating brain.Cellular and molecular life sciences : CMLS · 2025Article
- Effect of the MIAT/microRNA 130a-3p/Pdgfra axis on retinal microglia activation in mice with chronic retinal hypoperfusion injury.Cell biology and toxicology · 2025Article
- Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges.Cancers · 2024Review
- Control of OPC proliferation and repopulation by the intellectual disability gene PAK1 under homeostatic and demyelinating conditions.bioRxiv : the preprint server for biology · 2024Article
- Conditional Deletion ofInternational journal of molecular sciences · 2023Article
- Differential Early Mechanistic Frontal Lobe Responses to Choline Chloride and Soy Isoflavones in an Experimental Model of Fetal Alcohol Spectrum Disorder.International journal of molecular sciences · 2023Article
- Chronic oligodendrocyte injury in central nervous system pathologies.Communications biology · 2022Review
- High-Throughput Sequencing to Investigate lncRNA-circRNA-miRNA-mRNA Networks Underlying the Effects of Beta-Amyloid Peptide and Senescence on Astrocytes.Frontiers in genetics · 2022Article
- Prenatal overexpression of platelet-derived growth factor receptor A results in central nervous system hypomyelination.Brain and behavior · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPlatelet-derived growth factor (PDGF) signaling, through the ligand PDGF-A and its receptor PDGFRA, is important for the growth and maintenance of oligodendrocyte progenitor cells (OPCs) in the central nervous system (CNS). PDGFRA signaling is downregulated prior to OPC differentiation into mature myelinating oligodendrocytes. By contrast, PDGFRA is often genetically amplified or mutated in many types of gliomas, including diffuse midline glioma (DMG) where OPCs are considered the most likely cell-of-origin. The cellular and molecular changes that occur in OPCs in response to unregulated PDGFRA expression, however, are not known.
methodsHere, we created a conditional knock-in (KI) mouse that overexpresses wild type (WT) human PDGFRA (hPDGFRA) in prenatal Olig2-expressing progenitors, and examined in vivo cellular and molecular consequences.
resultsThe KI mice exhibited stunted growth, ataxia, and a severe loss of myelination in the brain and spinal cord. When combined with the loss of p53, a tumor suppressor gene whose activity is decreased in DMG, the KI mice failed to develop tumors but still exhibited hypomyelination. RNA-sequencing analysis revealed decreased myelination gene signatures, indicating a defect in oligodendroglial development. Mice overexpressing PDGFRA in prenatal GFAP-expressing progenitors, which give rise to a broader lineage of cells than Olig2-progenitors, also developed myelination defects.
conclusionOur results suggest that embryonic overexpression of hPDGFRA in Olig2- or GFAP-progenitors is deleterious to OPC development and leads to CNS hypomyelination.
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