Evidence map›Paper›PMID 25732776›Full record

ArticleDevelopmental biology2015

A 190 base pair, TGF-β responsive tooth and fin enhancer is required for stickleback Bmp6 expression.

Priscilla A Erickson, Phillip A Cleves, Nicholas A Ellis, Kevin T Schwalbach, James C Hart, Craig T Miller

Open access · greenAbstract read
In one paragraph

Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 32 citations in OpenAlex.

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  12. The genetic and molecular architecture of phenotypic diversity in sticklebacks.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
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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

6 authors at 1 institution in 1 country.

Priscilla A EricksonDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States.
Phillip A ClevesDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States.
Nicholas A EllisDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States.
Kevin T SchwalbachDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States.
James C HartDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States.
Craig T MillerDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States. Electronic address: ctmiller@berkeley.edu.
University of California, Berkeley · US

Funding

GENOMICST32HG000047 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI RASMUS NIELSEN, Daniel Soleyman Rokhsar · 2000 to 2026
$13.5M
Development Genetics of Tooth Number Variation in SticklebacksR01DE021475 · NIDCR · UNIVERSITY OF CALIFORNIA BERKELEY · PI MILLER, CRAIG THOMAS · 2011 to 2025
$5.4M
Developmental Genetics of Tooth Number Variation in SticklebacksR56DE021475 · NIDCR · UNIVERSITY OF CALIFORNIA BERKELEY · PI Craig Thomas Miller · 2026 to 2026
$349k
NHGRI NIH HHS T32 HG000047NIDCR NIH HHS R01 DE021475NIDCR NIH HHS R56 DE021475
6 · The paper itself

Abstract

The ligands of the Bone Morphogenetic Protein (BMP) family of developmental signaling molecules are often under the control of complex cis-regulatory modules and play diverse roles in vertebrate development and evolution. Here, we investigated the cis-regulatory control of stickleback Bmp6. We identified a 190bp enhancer ~2.5 kilobases 5' of the Bmp6 gene that recapitulates expression in developing teeth and fins, with a core 72bp sequence that is sufficient for both domains. By testing orthologous enhancers with varying degrees of sequence conservation from outgroup teleosts in transgenic reporter gene assays in sticklebacks and zebrafish, we found that the function of this regulatory element appears to have been conserved for over 250 million years of teleost evolution. We show that a predicted binding site for the TGFβ effector Smad3 in this enhancer is required for enhancer function and that pharmacological inhibition of TGFβ signaling abolishes enhancer activity and severely reduces endogenous Bmp6 expression. Finally, we used TALENs to disrupt the enhancer in vivo and find that Bmp6 expression is dramatically reduced in teeth and fins, suggesting this enhancer is necessary for expression of the Bmp6 locus. This work identifies a relatively short regulatory sequence that is required for expression in multiple tissues and, combined with previous work, suggests that shared regulatory networks control limb and tooth development.

Indexed as

Animal FinsAnimalsAnimals, Genetically ModifiedBase SequenceBenzamidesBinding SitesBone Morphogenetic Protein 6Chromosomes, Artificial, BacterialConserved SequenceDioxolesEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalHeterocyclic Compounds, 3-RingMolecular Sequence DataOdontogenesisReceptors, Transforming Growth Factor beta4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideBenzamidesBone Morphogenetic Protein 6DioxolesHeterocyclic Compounds, 3-RingReceptors, Transforming Growth Factor betaSmad3 ProteinXAV939Bmp6Bone morphogenetic proteinEnhancerSticklebackTGFßTooth developmentZebrafish

Identifiers

PMID25732776
PMCPMC4424077
OpenAlexW2073216818

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.