Evidence map›Paper›PMID 20460370›Full record

ArticleDevelopment (Cambridge, England)2010

The BMP pathway acts to directly regulate Tbx20 in the developing heart.

Elizabeth M Mandel, Erin Kaltenbrun, Thomas E Callis, Xin-Xin I Zeng, Sara R Marques, Deborah Yelon, Da-Zhi Wang, Frank L Conlon

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  9. Cold Spring Harbor perspectives in biology · 2020
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  11. Journal of biological research (Thessalonike, Greece) · 2019
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  12. Xenbase: Facilitating the Use ofFrontiers in physiology · 2019
    Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Differential regulation of CASZ1 protein expression during cardiac and skeletal muscle development.Developmental dynamics : an official publication of the American Association of Anatomists · 2014
    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

8 authors at 2 institutions in 1 country.

Elizabeth M MandelUniversity of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
Erin Kaltenbrun
Thomas E Callis
Xin-Xin I Zeng
Sara R Marques
Deborah Yelon
Da-Zhi Wang
Frank L Conlon
University of North Carolina Health Care · USUniversity of North Carolina at Chapel Hill · US

Funding

Craniofacial and cardiac development in Xenopus: A genetic approachR01DE018825 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CONLON, FRANK LEO, KHOKHA, MUSTAFA K · 2009 to 2013
$2.3M
TBX5 and cardiac proliferationR01HL089641 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CONLON, FRANK LEO · 2008 to 2011
$1.5M
NHLBI NIH HHS R01 HL089641NIDCR NIH HHS R01 DE018825
6 · The paper itself

Abstract

TBX20 has been shown to be essential for vertebrate heart development. Mutations within the TBX20 coding region are associated with human congenital heart disease, and the loss of Tbx20 in a wide variety of model systems leads to cardiac defects and eventually heart failure. Despite the crucial role of TBX20 in a range of cardiac cellular processes, the signal transduction pathways that act upstream of Tbx20 remain unknown. Here, we have identified and characterized a conserved 334 bp Tbx20 cardiac regulatory element that is directly activated by the BMP/SMAD1 signaling pathway. We demonstrate that this element is both necessary and sufficient to drive cardiac-specific expression of Tbx20 in Xenopus, and that blocking SMAD1 signaling in vivo specifically abolishes transcription of Tbx20, but not that of other cardiac factors, such as Tbx5 and MHC, in the developing heart. We further demonstrate that activation of Tbx20 by SMAD1 is mediated by a set of novel, non-canonical, high-affinity SMAD-binding sites located within this regulatory element and that phospho-SMAD1 directly binds a non-canonical SMAD1 site in vivo. Finally, we show that these non-canonical sites are necessary and sufficient for Tbx20 expression in Xenopus, and that reporter constructs containing these sites are expressed in a cardiac-specific manner in zebrafish and mouse. Collectively, our findings define Tbx20 as a direct transcriptional target of the BMP/SMAD1 signaling pathway during cardiac maturation.

Indexed as

AnimalsAnimals, Genetically ModifiedBase SequenceBinding SitesBone Morphogenetic ProteinsDNA PrimersGene Expression Regulation, DevelopmentalGenes, ReporterHeartHumansMiceMyocardiumSignal TransductionSmad ProteinsT-Box Domain ProteinsXenopusBone Morphogenetic ProteinsDNA PrimersSmad ProteinsT-Box Domain Proteins

Identifiers

PMID20460370
PMCPMC2867324
OpenAlexW1983079705

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.