Evidence map›Paper›PMID 26971948›Full record

ArticleNeuron2016

Psychiatric Risk Gene Transcription Factor 4 Regulates Intrinsic Excitability of Prefrontal Neurons via Repression of SCN10a and KCNQ1.

Matthew D Rannals, Gregory R Hamersky, Stephanie Cerceo Page, Morganne N Campbell, Aaron Briley, Ryan A Gallo, BaDoi N Phan, Thomas M Hyde, Joel E Kleinman, Joo Heon Shin and 3 more

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

Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 2 pooled it
13.5field-weighted citation impact, top 1% 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

68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  7. Article
  8. Applications of artificial intelligence in drug discovery for neurological diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
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  15. NovelFrontiers in physiology · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

8 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

13 authors at 2 institutions in 1 country.

Matthew D RannalsLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Gregory R HamerskyLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Stephanie Cerceo PageLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Morganne N CampbellLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Aaron BrileyLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Ryan A GalloLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
BaDoi N PhanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Thomas M HydeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Neurology and the McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Joel E KleinmanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Neurology and the McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Joo Heon ShinLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA.
Andrew E JaffeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Daniel R WeinbergerLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and the McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Brady J MaherLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address: brady.maher@libd.org.
Lieber Institute for Brain Development · USJohns Hopkins University · US

Funding

Cellular and Molecular Analysis of the Schizophrenia and Autism Spectrum Disorder gene Transcription Factor 4 (TCF4)R01MH110487 · NIMH · LIEBER INSTITUTE, INC. · PI MAHER, BRADY J · 2016 to 2024
$5.2M
Functional analysis of the Schizophrenia and Autism Spectrum Disorder gene TCF4 iR56MH104593 · NIMH · LIEBER INSTITUTE, INC. · PI MAHER, BRADY J · 2014 to 2015
$915k
The role of DISC 1 in synapse formation & function in the developing neocortexK01MH086050 · NIMH · UNIVERSITY OF CONNECTICUT STORRS · PI MAHER, BRADY J · 2009 to 2011
$522k
NIMH NIH HHS K01 MH086050NIMH NIH HHS K01MH086050NIMH NIH HHS R01 MH110487NIMH NIH HHS R56 MH104593NIMH NIH HHS R56MH104593
6 · The paper itself

Abstract

Transcription Factor 4 (TCF4) is a clinically pleiotropic gene associated with schizophrenia and Pitt-Hopkins syndrome (PTHS). To gain insight about the neurobiology of TCF4, we created an in vivo model of PTHS by suppressing Tcf4 expression in rat prefrontal neurons immediately prior to neurogenesis. This cell-autonomous genetic insult attenuated neuronal spiking by increasing the afterhyperpolarization. At the molecular level, using a novel technique called iTRAP that combined in utero electroporation and translating ribosome affinity purification, we identified increased translation of two ion channel genes, Kcnq1 and Scn10a. These ion channel candidates were validated by pharmacological rescue and molecular phenocopy. Remarkably, similar excitability deficits were observed in prefrontal neurons from a Tcf4(+/tr) mouse model of PTHS. Thus, we identify TCF4 as a regulator of neuronal intrinsic excitability in part by repression of Kcnq1 and Scn10a and suggest that this molecular function may underlie pathophysiology associated with neuropsychiatric disorders.

Indexed as

AnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCRISPR-Cas SystemsDisease Models, AnimalDNA-Binding ProteinsElectroporationFaciesFemaleGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseHaploinsufficiencyHyperventilationIntellectual DisabilityKCNQ1 Potassium ChannelMiceNAV1.8 Voltage-Gated Sodium ChannelBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDNA-Binding ProteinsKCNQ1 Potassium ChannelNAV1.8 Voltage-Gated Sodium ChannelRNA, MessengerRNA, Small InterferingTcf4 protein, mouseTcf4 protein, ratTranscription Factor 4Transcription Factors

Identifiers

PMID26971948
PMCPMC4824652
OpenAlexW2293408387

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.