Evidence map›Paper›PMID 22870402›Full record

ArticleG3 (Bethesda, Md.)2012

Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of Drosophila.

Dennis J Hazelett, Jer-Cherng Chang, Daniel L Lakeland, David B Morton

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.3field-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

35 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. BMP/TGF-β signaling as a modulator of neurodegeneration in ALS.Developmental dynamics : an official publication of the American Association of Anatomists · 2022
    Article
  6. Review
  7. Drosophila as a model to explore secondary injury cascades after traumatic brain injury.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021
    Review
  8. Review
  9. Article
  10. Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Overexpression ofAmerican journal of neurodegenerative disease · 2018
    Article
  20. Review
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

4 authors at 1 institution in 1 country.

Dennis J HazelettDepartment of Integrative Biosciences, Oregon Health & Science University, Portland, Oregon 97239, USA.
Jer-Cherng Chang
Daniel L Lakeland
David B Morton
Oregon Health & Science University · US

Funding

Using Drosophila as a model to understand TDP-43 function in ALSR21NS071186 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI MORTON, DAVID B · 2011 to 2012
$410k
NINDS NIH HHS NS071186NINDS NIH HHS R21 NS071186
6 · The paper itself

Abstract

The human Tar-DNA binding protein, TDP-43, is associated with amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. TDP-43 contains two conserved RNA-binding motifs and has documented roles in RNA metabolism, including pre-mRNA splicing and repression of transcription. Here, using Drosophila melanogaster as a model, we generated loss-of-function and overexpression genotypes of Tar-DNA binding protein homolog (TBPH) to study their effect on the transcriptome of the central nervous system (CNS). By using massively parallel sequencing methods (RNA-seq) to profile the CNS, we find that loss of TBPH results in widespread gene activation and altered splicing, much of which are reversed by rescue of TBPH expression. Conversely, TBPH overexpression results in decreased gene expression. Although previous studies implicated both absence and mis-expression of TDP-43 in ALS, our data exhibit little overlap in the gene expression between them, suggesting that the bulk of genes affected by TBPH loss-of-function and overexpression are different. In combination with computational approaches to identify likely TBPH targets and orthologs of previously identified vertebrate TDP-43 targets, we provide a comprehensive analysis of enriched gene ontologies. Our data suggest that TDP-43 plays a role in synaptic transmission, synaptic release, and endocytosis. We also uncovered a potential novel regulation of the Wnt and BMP pathways, many of whose targets appear to be conserved.

Indexed as

Gene Expression RegulationAnimalsBinding SitesCentral Nervous SystemCluster AnalysisDNA-Binding ProteinsDrosophila melanogasterDrosophila ProteinsGenotypeHigh-Throughput Nucleotide SequencingRNA SplicingDNA-Binding ProteinsDrosophila Proteinsgenomicsinvertebrate models of human diseaseneurodegenerationneuropathyRNA binding proteinTARDBP

Identifiers

PMID22870402
PMCPMC3385985
OpenAlexW1970606504

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.