Evidence map›Paper›PMID 26657204›Full record

ArticleScientific reports2015

MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome.

Elena Chiavacci, Romina D'Aurizio, Elena Guzzolino, Francesco Russo, Mario Baumgart, Marco Groth, Laura Mariani, Mara D'Onofrio, Ivan Arisi, Marco Pellegrini and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. From Stripes to a Beating Heart: Early Cardiac Development in Zebrafish.Journal of cardiovascular development and disease · 2021
    Review
  6. Review
  7. Article
  8. Article
  9. Dysregulated micro-RNAs and long noncoding RNAs in cardiac development and pediatric heart failure.American journal of physiology. Heart and circulatory physiology · 2020
    Review
  10. Epigenetic Regulation of Organ Regeneration in Zebrafish.Journal of cardiovascular development and disease · 2018
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. 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

13 authors.

Elena ChiavacciInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, Italy.
Romina D'AurizioLaboratory of Integrative Systems Medicine (LISM), Institute of Informatics andTelematics (IIT) and Institute of Clinical Physiology (IFC), (CNR), Pisa, Italy.
Elena GuzzolinoInstitute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy.
Francesco RussoLaboratory of Integrative Systems Medicine (LISM), Institute of Informatics andTelematics (IIT) and Institute of Clinical Physiology (IFC), (CNR), Pisa, Italy.
Mario BaumgartLeibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745 Jena, Germany.
Marco GrothLeibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745 Jena, Germany.
Laura MarianiInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, Italy.
Mara D'OnofrioGenomics Facility, European Brain Research Institute, Via del Fosso di Fiorano 64 00143 Roma, Italy.
Ivan ArisiGenomics Facility, European Brain Research Institute, Via del Fosso di Fiorano 64 00143 Roma, Italy.
Marco PellegriniLaboratory of Integrative Systems Medicine (LISM), Institute of Informatics andTelematics (IIT) and Institute of Clinical Physiology (IFC), (CNR), Pisa, Italy.
Alessandro CellerinoScuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy.
Federico CremisiScuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy.
Letizia PittoInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Holt-Oram Syndrome (HOS) is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene, a transcription factor capable of regulating hundreds of cardiac-specific genes through complex transcriptional networks. Here we show that, in zebrafish, modulation of a single miRNA is sufficient to rescue the morphogenetic defects generated by HOS. The analysis of miRNA-seq profiling revealed a decreased expression of miR-19a in Tbx5-depleted zebrafish embryos compared to the wild type. We revealed that the transcription of the miR-17-92 cluster, which harbors miR-19a, is induced by Tbx5 and that a defined dosage of miR-19a is essential for the correct development of the heart. Importantly, we highlighted that miR-19a replacement is able to rescue cardiac and pectoral fin defects and to increase the viability of HOS zebrafish embryos. We further observed that miR-19a replacement shifts the global gene expression profile of HOS-like zebrafish embryos towards the wild type condition, confirming the ability of miR-19a to rescue the Tbx5 phenotype. In conclusion our data demonstrate the importance of Tbx5/miR-19a regulatory circuit in heart development and provide a proof of principle that morphogenetic defects associated with HOS can be rescued by transient miRNA modulation.

Indexed as

Genetic TherapyPhenotypeRNA InterferenceAbnormalities, MultipleAnimal FinsAnimalsEmbryonic DevelopmentGene Expression Regulation, DevelopmentalGenome-Wide Association StudyGenomicsHeart Defects, CongenitalHeart Septal Defects, AtrialLower Extremity Deformities, CongenitalMicroRNAsMultigene FamilyT-Box Domain ProteinsMicroRNAsT-Box Domain ProteinsT-box transcription factor 5

Identifiers

PMID26657204
PMCPMC4677400

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Registered trials

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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.