Evidence map›Paper›PMID 24316074›Full record

ArticleCell reports2013

High-throughput genetic screen for synaptogenic factors: identification of LRP6 as critical for excitatory synapse development.

Kamal Sharma, Se-Young Choi, Yong Zhang, Thomas J F Nieland, Shunyou Long, Min Li, Richard L Huganir

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

Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

34 citing papers in PubMed, 54 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Kamal SharmaDepartment of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Se-Young ChoiDepartment of Physiology, Seoul National University School of Dentistry, Seoul 110-749, South Korea.
Yong ZhangDepartment of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Thomas J F NielandStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
Shunyou LongDepartment of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Min LiDepartment of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Richard L HuganirDepartment of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: rhuganir@jhmi.edu.
Johns Hopkins University · USBroad Institute · USSeoul National University · KR

Funding

Johns Hopkins Ion Channel CenterU54MH084691 · NIMH · JOHNS HOPKINS UNIVERSITY · PI LI, MIN · 2008 to 2012
$13.9M
Murine Mutagenesis CoreP30NS050274 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOLODKIN, ALEX L · 2005 to 2020
$10.9M
High Throughput Screen for Small Molecule Probes for Neural Network DevelopmentR01MH095058 · NIMH · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 2011 to 2014
$1.6M
Howard Hughes Medical InstituteNIMH NIH HHS 5U54MH084691NIMH NIH HHS R01 MH095058NIMH NIH HHS U54 MH084691NINDS NIH HHS P30 NS050274
6 · The paper itself

Abstract

Genetic screens in invertebrates have discovered many synaptogenic genes and pathways. However, similar genetic studies have not been possible in mammals. We have optimized an automated high-throughput platform that employs automated liquid handling and imaging of primary mammalian neurons. Using this platform, we have screened 3,200 shRNAs targeting 800 proteins. One of the hits identified was LRP6, a coreceptor for canonical Wnt ligands. LRP6 regulates excitatory synaptogenesis and is selectively localized to excitatory synapses. In vivo knockdown of LRP6 leads to a reduction in the number of functional synapses. Moreover, we show that the canonical Wnt ligand, Wnt8A, promotes synaptogenesis via LRP6. These results provide a proof of principle for using a high-content approach to screen for synaptogenic factors in the mammalian nervous system and identify and characterize a Wnt ligand receptor complex that is critical for the development of functional synapses in vivo.

Indexed as

AnimalsCloning, MolecularCyclic AMP Response Element-Binding ProteinHEK293 CellsHigh-Throughput Screening AssaysHippocampusHumansIntercellular Signaling Peptides and ProteinsLigandsLow Density Lipoprotein Receptor-Related Protein-6MiceNeuronsOptical ImagingProtein BindingRatsRNA, Small InterferingCyclic AMP Response Element-Binding ProteinIntercellular Signaling Peptides and ProteinsLigandsLow Density Lipoprotein Receptor-Related Protein-6RNA, Small Interfering

Identifiers

PMID24316074
PMCPMC3924421
OpenAlexW2023467539

What OpenQuestion holds

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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.