Evidence map›Paper›PMID 23775563›Full record

ArticleMolecular pharmacology2013

Sox9b is required for epicardium formation and plays a role in TCDD-induced heart malformation in zebrafish.

Peter Hofsteen, Jessica Plavicki, Shaina D Johnson, Richard E Peterson, Warren Heideman

Open access · bronzeAbstract read
In one paragraph

Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. The Ahr2-Dependent wfikkn1 Gene Influences Zebrafish Transcriptome, Proteome, and Behavior.Toxicological sciences : an official journal of the Society of Toxicology · 2022
    Article
  9. Article
  10. Article
  11. Article
  12. A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors.Toxicological sciences : an official journal of the Society of Toxicology · 2020
    Review
  13. Article
  14. Non-pathological Chondrogenic Features of Valve Interstitial Cells in Normal Adult Zebrafish.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019
    Article
  15. Mechanisms of Developmental Toxicity of Dioxins and Related Compounds.International journal of molecular sciences · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

5 authors at 1 institution in 1 country.

Peter HofsteenDivision of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, USA.
Jessica Plavicki
Shaina D Johnson
Richard E Peterson
Warren Heideman
University of Wisconsin–Madison · US

Funding

Molecular & Environmental Toxicology Pre-& Postdoctoral Training ProgramT32ES007015 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI CHRISTOPHER A BRADFIELD · 1985 to 2026
$11.5M
TCDD- INDUCED CARDIOTOXICITY IN DEVELOPING ZEBRAFISHR01ES012716 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI HEIDEMAN, WARREN NO MIDDLE NAME · 2005 to 2015
$2.7M
NIEHS NIH HHS R01 ES012716NIEHS NIH HHS T32 ES007015
6 · The paper itself

Abstract

Activation of the transcription factor aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the formation of the epicardium and leads to severe heart malformations in developing zebrafish (Danio rerio). The downstream genes that cause heart malformation are not known. Because TCDD causes craniofacial malformations in zebrafish by downregulating the sox9b gene, we hypothesized that cardiotoxicity might also result from sox9b downregulation. We found that sox9b is expressed in the developing zebrafish heart ventricle and that TCDD exposure markedly reduces this expression. Furthermore, we found that manipulation of sox9b expression could phenocopy many but not all of the effects of TCDD at the heart. Loss of sox9b prevented the formation of epicardium progenitors comprising the proepicardium on the pericardial wall, and prevented the formation and migration of the epicardial layer around the heart. Zebrafish lacking sox9b showed pericardial edema, an elongated heart, and reduced blood circulation. Fish lacking sox9b failed to form valve cushions and leaflets. Sox9b is one of two mammalian Sox9 homologs, sox9b and sox9a. Knock down of sox9a expression did not cause cardiac malformations, or defects in epicardium development. We conclude that the decrease in sox9b expression in the heart caused by TCDD plays a role in many of the observed signs of cardiotoxicity. We find that while sox9b is expressed in myocardial cells, it is not normally expressed in the affected epicardial cells or progenitors. We therefore speculate that sox9b is involved in signals between the cardiomyocytes and the nascent epicardial cells.

Indexed as

Abnormalities, Drug-InducedAnimalsCoronary CirculationDown-RegulationEdemaHeart Defects, CongenitalHeart ValvesHeart VentriclesMyocytes, CardiacPericardiumPolychlorinated DibenzodioxinsSOX9 Transcription FactorZebrafishZebrafish ProteinsPolychlorinated DibenzodioxinsSox9b protein, zebrafishSOX9 Transcription FactorZebrafish Proteins

Identifiers

PMID23775563
PMCPMC3876814
OpenAlexW2125541269

What OpenQuestion holds

Textmetadata
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.