Evidence map›Paper›PMID 26523971›Full record

ArticleNature medicine2015

An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development.

Seung Tae Baek, Brett Copeland, Eun-Jin Yun, Seok-Kyu Kwon, Alicia Guemez-Gamboa, Ashleigh E Schaffer, Sangwoo Kim, Hoon-Chul Kang, Saera Song, Gary W Mathern and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
10.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.

  1. Pooled it
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  7. Article
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  9. Article
  10. PLP1-Targeting Antisense Oligonucleotides Improve FOXG1 Syndrome Mice.International journal of molecular sciences · 2024
    Article
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  12. Article
  13. Article
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  16. Anti-seizure gene therapy for focal cortical dysplasia.Brain : a journal of neurology · 2024
    Article
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  18. Review
  19. Rett and Rett-related disorders: Common mechanisms for shared symptoms?Experimental biology and medicine (Maywood, N.J.) · 2023
    Review
  20. Review

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 2 countries.

Seung Tae BaekLaboratory of Pediatric Brain Diseases, Rockefeller University, New York, New York, USA.ORCID http://orcid.org/0000-0003-0040-1501
Brett CopelandLaboratory of Pediatric Brain Diseases, Rockefeller University, New York, New York, USA.
Eun-Jin YunDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Seok-Kyu KwonDepartment of Neuroscience, Columbia University, New York, New York, USA.
Alicia Guemez-GamboaLaboratory of Pediatric Brain Diseases, Rockefeller University, New York, New York, USA.
Ashleigh E SchafferDepartment of Neurosciences, University of California San Diego (UCSD), La Jolla, California, USA.
Sangwoo KimSeverance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
Hoon-Chul KangLaboratory of Pediatric Brain Diseases, Rockefeller University, New York, New York, USA.
Saera SongLaboratory of Pediatric Brain Diseases, Rockefeller University, New York, New York, USA.
Gary W MathernDepartment of Neurosurgery, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Joseph G GleesonLaboratory of Pediatric Brain Diseases, Rockefeller University, New York, New York, USA.
Rockefeller University · USUniversity of California San Diego · USYonsei University · KRColumbia University · USHoward Hughes Medical Institute · USThe University of Texas Southwestern Medical Center · USUniversity of California, Los Angeles · US

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Mosaicism in focal cortical dysplasias spectrum seen in neuropsychiatric diseaseU01MH108898 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2015 to 2019
$5.1M
Molecular characterization of HemimegalencephalyR01NS083823 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, MATHERN, GARY W. · 2013 to 2017
$3.1M
Molecular Mechanisms of Intellectual DisabilityK99HD082337 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHAFFER, ASHLEIGH E · 2015 to 2016
$268k
Howard Hughes Medical InstituteNICHD NIH HHS K99 HD082337NICHD NIH HHS K99HD082337NIMH NIH HHS U01 MH108898NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS083823NINDS NIH HHS R01NS083823
6 · The paper itself

Abstract

Focal malformations of cortical development (FMCDs) account for the majority of drug-resistant pediatric epilepsy. Postzygotic somatic mutations activating the phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway are found in a wide range of brain diseases, including FMCDs. It remains unclear how a mutation in a small fraction of cells disrupts the architecture of the entire hemisphere. Within human FMCD-affected brain, we found that cells showing activation of the PI3K-AKT-mTOR pathway were enriched for the AKT3(E17K) mutation. Introducing the FMCD-causing mutation into mouse brain resulted in electrographic seizures and impaired hemispheric architecture. Mutation-expressing neural progenitors showed misexpression of reelin, which led to a non-cell autonomous migration defect in neighboring cells, due at least in part to derepression of reelin transcription in a manner dependent on the forkhead box (FOX) transcription factor FOXG1. Treatments aimed at either blocking downstream AKT signaling or inactivating reelin restored migration. These findings suggest a central AKT-FOXG1-reelin signaling pathway in FMCD and support pathway inhibitors as potential treatments or therapies for some forms of focal epilepsy.

Indexed as

Cell MovementAnimalsBase SequenceCell Adhesion Molecules, NeuronalCell DifferentiationDisease Models, AnimalEnzyme ActivationExtracellular Matrix ProteinsForkhead Transcription FactorsGene Expression Regulation, DevelopmentalGene Regulatory NetworksGreen Fluorescent ProteinsHumansMagnetic Resonance ImagingMalformations of Cortical DevelopmentMiceAKT3 protein, humanCell Adhesion Molecules, NeuronalExtracellular Matrix ProteinsForkhead Transcription FactorsFOXG1 protein, humanGreen Fluorescent ProteinsMTOR protein, humanNerve Tissue ProteinsProto-Oncogene Proteins c-aktReelin ProteinRELN protein, humanReln protein, mouseRNA, Small InterferingSerine EndopeptidasesTOR Serine-Threonine Kinases

Identifiers

PMID26523971
PMCPMC4955611
OpenAlexW1919859028

What OpenQuestion holds

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Registered trials

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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.