Evidence map›Paper›PMID 24496616›Full record

ArticleDevelopment (Cambridge, England)2014

Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.

Carolina Barcellos Machado, Kevin C Kanning, Patricia Kreis, Danielle Stevenson, Martin Crossley, Magdalena Nowak, Michelina Iacovino, Michael Kyba, David Chambers, Eric Blanc and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
1.7field-weighted citation impact, top 18% 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, 56 citations in OpenAlex.

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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Carolina Barcellos MachadoMRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, UK.
Kevin C Kanning
Patricia Kreis
Danielle Stevenson
Martin Crossley
Magdalena Nowak
Michelina Iacovino
Michael Kyba
David Chambers
Eric Blanc
Ivo Lieberam
King's College London · GBColumbia University · USMinneapolis Heart Institute Foundation · USUniversity of Minnesota · US

Funding

Biotechnology and Biological Sciences Research Council G1001234Medical Research Council G0900585Medical Research Council G0901899
6 · The paper itself

Abstract

Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.

Indexed as

AnimalsCadherinsCell DifferentiationDiaphragmEmbryonic Stem CellsFlow CytometryHomeodomain ProteinsMiceMotor NeuronsOctamer Transcription Factor-6PhosphoproteinsPhrenic NerveProtocadherinsReal-Time Polymerase Chain ReactionReceptors, NotchSignal TransductionCadherinsCdh10 protein, mouseHomeodomain ProteinsHoxa5 protein, mouseOctamer Transcription Factor-6Pcdh10 protein, mousePhosphoproteinsPou3f1 protein, mouseProtocadherinsReceptors, NotchTranscription FactorsEmbryonic stem cellMotor neuron differentiationPhrenic neuronTranscriptional identity

Identifiers

PMID24496616
PMCPMC3912827
OpenAlexW2067003262

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.