Evidence map›Paper›PMID 23152446›Full record

ArticleGenes & development2012

Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis.

Alexandre R Colas, Wesley L McKeithan, Thomas J Cunningham, Paul J Bushway, Lana X Garmire, Gregg Duester, Shankar Subramaniam, Mark Mercola

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
–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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
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  13. Let-7f promotes the differentiation of neural stem cells in rats.American journal of translational research · 2020
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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

8 authors at 1 institution in 1 country.

Alexandre R ColasSanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Wesley L McKeithan
Thomas J Cunningham
Paul J Bushway
Lana X Garmire
Gregg Duester
Shankar Subramaniam
Mark Mercola
Sanford Burnham Prebys Medical Discovery Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Generation of Retinoid Signals During DevelopmentR01GM062848 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI DUESTER, GREGG L · 2002 to 2015
$4.6M
microRNAs and Integrative Control on Cardiopoiesis - CHANGE OF GRANTEE INSTITUTIOR01HL113601 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MERCOLA, MARK · 2012 to 2016
$2.2M
Reconstruction and Modeling of Networks Involved in Cardiomyoctye DifferentiationR33HL087375 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2007 to 2009
$1.1M
Reconstruction & Modeling of Networks Involved in Cardiomyocyte DifferentiationR33HL088266 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MERCOLA, MARK · 2007 to 2009
$1.0M
NCI NIH HHS P30 CA030199NCI NIH HHS P30 CA030199-30NHLBI NIH HHS R01 HL113601NHLBI NIH HHS R33 HL087375NHLBI NIH HHS R33 HL088266NIGMS NIH HHS R01 GM062848
6 · The paper itself

Abstract

Tight control over the segregation of endoderm, mesoderm, and ectoderm is essential for normal embryonic development of all species, yet how neighboring embryonic blastomeres can contribute to different germ layers has never been fully explained. We postulated that microRNAs, which fine-tune many biological processes, might modulate the response of embryonic blastomeres to growth factors and other signals that govern germ layer fate. A systematic screen of a whole-genome microRNA library revealed that the let-7 and miR-18 families increase mesoderm at the expense of endoderm in mouse embryonic stem cells. Both families are expressed in ectoderm and mesoderm, but not endoderm, as these tissues become distinct during mouse and frog embryogenesis. Blocking let-7 function in vivo dramatically affected cell fate, diverting presumptive mesoderm and ectoderm into endoderm. siRNA knockdown of computationally predicted targets followed by mutational analyses revealed that let-7 and miR-18 down-regulate Acvr1b and Smad2, respectively, to attenuate Nodal responsiveness and bias blastomeres to ectoderm and mesoderm fates. These findings suggest a crucial role for the let-7 and miR-18 families in germ layer specification and reveal a remarkable conservation of function from amphibians to mammals.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsCells, CulturedDNA Mutational AnalysisEmbryonic DevelopmentEmbryonic Stem CellsGene Knockdown TechniquesGenomeGerm LayersMiceMicroRNAsXenopus laevisMicroRNAsMIRN18 microRNA, mousemirnlet7 microRNA, mouse

Identifiers

PMID23152446
PMCPMC3521625
OpenAlexW2146242051

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.