Evidence map›Paper›PMID 36696714›Full record

ArticleDevelopmental biology2023

Zebrafish her3 knockout impacts developmental and cancer-related gene signatures.

Matthew R Kent, Delia Calderon, Katherine M Silvius, Jack P Kucinski, Collette A LaVigne, Matthew V Cannon, Genevieve C Kendall

Open access · hybridAbstract read
In one paragraph

Article in Developmental biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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  13. Epigenetic determinants of fusion-driven sarcomas: paradigms and challenges.Frontiers in cell and developmental biology · 2024
    Article
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 2 institutions in 1 country.

Matthew R KentCenter for Childhood Cancer & Blood Diseases, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Delia CalderonCenter for Childhood Cancer & Blood Diseases, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA; Molecular, Cellular, and Developmental Biology Ph.D. Program, The Ohio State University, Columbus, OH, 43210, USA.
Katherine M SilviusCenter for Childhood Cancer & Blood Diseases, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Jack P KucinskiCenter for Childhood Cancer & Blood Diseases, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA; Molecular, Cellular, and Developmental Biology Ph.D. Program, The Ohio State University, Columbus, OH, 43210, USA.
Collette A LaVigneDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Matthew V CannonCenter for Childhood Cancer & Blood Diseases, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Genevieve C KendallCenter for Childhood Cancer & Blood Diseases, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA; Molecular, Cellular, and Developmental Biology Ph.D. Program, The Ohio State University, Columbus, OH, 43210, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, 43205, USA. Electronic address: Genevieve.Kendall@NationwideChildrens.org.
Nationwide Children's Hospital · USSouthwestern Medical Center · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Understanding Infantile Rhabdomyosarcoma Biology and Therapeutic TargetsR01CA272872 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI Genevieve Claire Kendall · 2022 to 2026
$2.1M
Training Program in Basic and Translational Pediatric Oncology ResearchT32CA269052 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI TIMOTHY P CRIPE · 2022 to 2026
$1.8M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA272872NCI NIH HHS T32 CA269052
6 · The paper itself

Abstract

HES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle. However, the mechanisms of HES3 cooperation in fusion-positive rhabdomyosarcoma are unclear and are likely related to her3/HES3's role in neurogenesis. To investigate HES3's function during development, we generated a zebrafish CRISPR/Cas9 null mutation of her3, the zebrafish ortholog of HES3. Loss of her3 is not embryonic lethal and adults exhibit expected Mendelian ratios. Embryonic her3 zebrafish mutants exhibit dysregulated neurog1 expression, a her3 target gene, and the mutant her3 fails to bind the neurog1 promoter sequence. Further, her3 mutants are significantly smaller than wildtype and a subset present with lens defects as adults. Transcriptomic analysis of her3 mutant embryos indicates that genes involved in organ development, such as pctp and grinab, are significantly downregulated. Further, differentially expressed genes in her3 null mutant embryos are enriched for Hox and Sox10 motifs. Several cancer-related gene pathways are impacted, including the inhibition of matrix metalloproteinases. Altogether, this new model is a powerful system to study her3/HES3-mediated neural development and its misappropriation in cancer contexts.

Indexed as

RhabdomyosarcomaZebrafishAnimalsBasic Helix-Loop-Helix ProteinsGene Expression Regulation, DevelopmentalNervous SystemNeurogenesisRepressor ProteinsZebrafish ProteinsBasic Helix-Loop-Helix ProteinsHer3 protein, zebrafishRepressor ProteinsZebrafish ProteinsCRISPR/Cas9 knockoutFunctional genomicsHer3/HES3Neural developmentTranscriptomicsZebrafish

Identifiers

PMID36696714
PMCPMC10054701
OpenAlexW4318167643

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.