Evidence map›Paper›PMID 26283362›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs.

Siew Fen Lisa Wong, Vikram Agarwal, Jennifer H Mansfield, Nicolas Denans, Matthew G Schwartz, Haydn M Prosser, Olivier Pourquié, David P Bartel, Clifford J Tabin, Edwina McGlinn

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

37 citing papers in PubMed, 70 citations in OpenAlex.

  1. Evaluating the reliability of tools for mRNA annotation and IRES studies.bioRxiv : the preprint server for biology · 2026
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  6. CTCF-dependent insulation ofProceedings of the National Academy of Sciences of the United States of America · 2024
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  9. The expanding roles of Nr6a1 in development and evolution.Frontiers in cell and developmental biology · 2024
    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

10 authors at 7 institutions in 3 countries.

Siew Fen Lisa WongEMBL Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia;
Vikram AgarwalHoward Hughes Medical Institute, Cambridge, MA 02142; Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139;
Jennifer H MansfieldDepartment of Genetics, Harvard Medical School, Boston, MA 02115; Department of Biological Sciences, Barnard College, New York, NY 10027;
Nicolas DenansDepartment of Developmental Biology and Genetics, Stanford School of Medicine, Stanford, CA 94305;
Matthew G SchwartzDepartment of Genetics, Harvard Medical School, Boston, MA 02115;
Haydn M ProsserThe Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
Olivier PourquiéDepartment of Genetics, Harvard Medical School, Boston, MA 02115; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
David P BartelHoward Hughes Medical Institute, Cambridge, MA 02142; Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
Clifford J TabinDepartment of Genetics, Harvard Medical School, Boston, MA 02115; tabin@genetics.med.harvard.edu edwina.mcglinn@emblaustralia.org.
Edwina McGlinnEMBL Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia; Department of Genetics, Harvard Medical School, Boston, MA 02115; tabin@genetics.med.harvard.edu edwina.mcglinn@emblaustralia.org.
Harvard University · USAustralian Regenerative Medicine Institute · AUBrigham and Women's Hospital · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · USStanford University · USWellcome Sanger Institute · GB

Funding

MicroRNA genes and their functionsR01GM067031 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI BARTEL, DAVID P · 2002 to 2015
$7.3M
Hedgehog Signaling and Organogenesis of the LimbR37HD032443 · NICHD · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI TABIN, CLIFFORD J. · 2005 to 2014
$5.3M
Howard Hughes Medical InstituteNICHD NIH HHS R37 HD032443NICHD NIH HHS R37HD032443-19NIGMS NIH HHS GM067031NIGMS NIH HHS R01 GM067031Wellcome Trust 098051
6 · The paper itself

Abstract

The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3' UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae.

Indexed as

AnimalsGene DeletionMiceMice, KnockoutMicroRNAsSpineTranscription, GeneticTranscriptomeMicroRNAsMIRN196 microRNA, mouseaxial patterningHox genesmicroRNAmiR-196vertebral specification

Identifiers

PMID26283362
PMCPMC4568285
OpenAlexW2108432715

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.