ArticleCerebral cortex (New York, N.Y. : 1991)2021
Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.
Article in Cerebral cortex (New York, N.Y. : 1991), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Establishing mouse forebrain organoids as models of intrinsic cortical network assembly.Stem cell reports · 2026Article
- Fate plasticity of interneuron specification.iScience · 2025Article
- Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models.The Journal of clinical investigation · 2025Article
- Transcriptomic Dysregulation in Animal Models of Attention-Deficit Hyperactivity Disorder and Nicotine Dependence Suggests Shared Neural Mechanisms.Brain and behavior · 2025Article
- Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus.Molecular psychiatry · 2024Article
- Neurotrophins and Their Receptors: BDNF's Role in GABAergic Neurodevelopment and Disease.International journal of molecular sciences · 2024Review
- Hyperactivation of MEK1 in cortical glutamatergic neurons results in projection axon deficits and aberrant motor learning.Disease models & mechanisms · 2024Article
- Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs.Development (Cambridge, England) · 2023Article
- Cellular signaling impacts upon GABAergic cortical interneuron development.Frontiers in neuroscience · 2023Review
- Dose-dependent seizure control with MEK inhibitor therapy for progressive glioma in a child with neurofibromatosis type 1.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- The Impact of Maternal Antioxidants on Prenatal Stress Effects on Offspring Neurobiology and Behavior.The Yale journal of biology and medicine · 2022Article
- Review
- Chromatin remodeller CHD7 is required for GABAergic neuron development by promoting PAQR3 expression.EMBO reports · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development of GABAergic cortical interneurons (CINs), a heterogeneous population of inhibitory neurons necessary for cortical function. We show that GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling in a subpopulation of immature neurons in the embryonic subpallial mantle zone. Adult mutants displayed a significant loss of parvalbumin (PV), but not somatostatin, expressing CINs and a reduction in perisomatic inhibitory synapses on excitatory neurons. Surviving mutant PV-CINs maintained a typical fast-spiking phenotype but showed signs of decreased intrinsic excitability that coincided with an increased risk of seizure-like phenotypes. In contrast to other mouse models of PV-CIN loss, we discovered a robust increase in the accumulation of perineuronal nets, an extracellular structure thought to restrict plasticity. Indeed, we found that mutants exhibited a significant impairment in the acquisition of behavioral response inhibition capacity. Overall, our data suggest PV-CIN development is particularly sensitive to hyperactive MEK1 signaling, which may underlie certain neurological deficits frequently observed in ERK/MAPK-linked syndromes.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.