ArticlePLoS genetics2019
The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Social Communication in Ras Pathway Disorders: A Comprehensive Review From Genetics to Behavior in Neurofibromatosis Type 1 and Noonan Syndrome.Biological psychiatry · 2025Pooled it
- Quantitative T1 Mapping Indicates Elevated White Matter Myelin in Children With RASopathies.Biological psychiatry · 2025Article
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- Genotype-phenotype correlations with autism spectrum disorder-related traits in noonan syndrome and noonan syndrome with multiple lentigines: a cross-sectional study.Molecular autism · 2025Article
- Current states in understanding oligodendroglia-mediated neurological issues in neurofibromatosis type 1 (NF1).Acta neuropathologica communications · 2025Review
- Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models.The Journal of clinical investigation · 2025Article
- Targeting Shp2 as a therapeutic strategy for neurodegenerative diseases.Translational psychiatry · 2025Review
- Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor.Molecular medicine (Cambridge, Mass.) · 2024Article
- Deciphering Oligodendrocyte Lineages in the Human Fetal Central Nervous System Using Single-Cell RNA Sequencing.Molecular neurobiology · 2024Article
- Interactions between Ras and Rap signaling pathways during neurodevelopment in health and disease.Frontiers in molecular neuroscience · 2024Review
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- Review
- A role for sustained MAPK activity in the mouse ventral telencephalon.Developmental biology · 2021Article
- MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders.Molecular autism · 2021Article
- Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Age Impacts the Burden That Reference Memory Imparts on an Increasing Working Memory Load and Modifies Relationships With Cholinergic Activity.Frontiers in behavioral neuroscience · 2021Article
- Generation of a Mouse Model to Study the Noonan Syndrome GeneFrontiers in cell and developmental biology · 2021Article
- Neuron type-specific expression of a mutant KRAS impairs hippocampal-dependent learning and memory.Scientific reports · 2020Article
- SHP2 mutations induce precocious gliogenesis of Noonan syndrome-derived iPSCs during neural development in vitro.Stem cell research & therapy · 2020Article
- Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
RASopathies are a family of related syndromes caused by mutations in regulators of the RAS/Extracellular Regulated Kinase 1/2 (ERK1/2) signaling cascade that often result in neurological deficits. RASopathy mutations in upstream regulatory components, such as NF1, PTPN11/SHP2, and RAS have been well-characterized, but mutation-specific differences in the pathogenesis of nervous system abnormalities remain poorly understood, especially those involving mutations downstream of RAS. Here, we assessed cellular and behavioral phenotypes in mice expressing a Raf1L613V gain-of-function mutation associated with the RASopathy, Noonan Syndrome. We report that Raf1L613V/wt mutants do not exhibit a significantly altered number of excitatory or inhibitory neurons in the cortex. However, we observed a significant increase in the number of specific glial subtypes in the forebrain. The density of GFAP+ astrocytes was significantly increased in the adult Raf1L613V/wt cortex and hippocampus relative to controls. OLIG2+ oligodendrocyte progenitor cells were also increased in number in mutant cortices, but we detected no significant change in myelination. Behavioral analyses revealed no significant changes in voluntary locomotor activity, anxiety-like behavior, or sociability. Surprisingly, Raf1L613V/wt mice performed better than controls in select aspects of the water radial-arm maze, Morris water maze, and cued fear conditioning tasks. Overall, these data show that increased astrocyte and oligodendrocyte progenitor cell (OPC) density in the cortex coincides with enhanced cognition in Raf1L613V/wt mutants and further highlight the distinct effects of RASopathy mutations on nervous system development and function.
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Registered trials
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