Evidence map›Paper›PMID 28007784›Full record

ArticleGenes & development2016

An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons.

Elena Appel, Sarit Weissmann, Yehuda Salzberg, Kira Orlovsky, Varda Negreanu, Michael Tsoory, Calanit Raanan, Ester Feldmesser, Yael Bernstein, Orit Wolstein and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2016. 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, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Influencers in the Somatosensory System: Extrinsic Control of Sensory Neuron Phenotypes.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. New functions for the proprioceptive system in skeletal biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018
    Review
  12. Article
  13. Molecular mechanisms underlying monosynaptic sensory-motor circuit development in the spinal cord.Developmental dynamics : an official publication of the American Association of Anatomists · 2018
    Review
  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

12 authors at 1 institution in 1 country.

Elena AppelDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Sarit WeissmannDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Yehuda SalzbergDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Kira OrlovskyDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Varda NegreanuDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Michael TsooryDepartment of Veterinary Resources, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Calanit RaananDepartment of Veterinary Resources, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Ester FeldmesserLife Science Core Facilities, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Yael BernsteinDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Orit WolsteinDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Ditsa LevanonDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Yoram GronerDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
Weizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Runx3 transcription factor is essential for development and diversification of the dorsal root ganglia (DRGs) TrkC sensory neurons. In Runx3-deficient mice, developing TrkC neurons fail to extend central and peripheral afferents, leading to cell death and disruption of the stretch reflex circuit, resulting in severe limb ataxia. Despite its central role, the mechanisms underlying the spatiotemporal expression specificities of Runx3 in TrkC neurons were largely unknown. Here we first defined the genomic transcription unit encompassing regulatory elements (REs) that mediate the tissue-specific expression of Runx3. Using transgenic mice expressing BAC reporters spanning the Runx3 locus, we discovered three REs-dubbed R1, R2, and R3-that cross-talk with promoter-2 (P2) to drive TrkC neuron-specific Runx3 transcription. Deletion of single or multiple elements either in the BAC transgenics or by CRISPR/Cas9-mediated endogenous ablation established the REs' ability to promote and/or repress Runx3 expression in developing sensory neurons. Our analysis reveals that an intricate combinatorial interplay among the three REs governs Runx3 expression in distinct subtypes of TrkC neurons while concomitantly extinguishing its expression in non-TrkC neurons. These findings provide insights into the mechanism regulating cell type-specific expression and subtype diversification of TrkC neurons in developing DRGs.

Indexed as

AnimalsAtaxiaBinding SitesCore Binding Factor Alpha 3 SubunitEmbryo, MammalianGanglia, SpinalGene DeletionGene Expression Regulation, DevelopmentalLocomotionMaleMiceMice, TransgenicNeuronsPromoter Regions, GeneticProtein BindingRegulatory Elements, TranscriptionalCore Binding Factor Alpha 3 SubunitRunx3 protein, mouseTranscription FactorsBAC transgenic miceCRISPR/Cas9 enhancer mutantsDRG TrkC proprioceptive neuronslong-range transcription regulatory elementsRunx3 transcription factor

Identifiers

PMID28007784
PMCPMC5204353
OpenAlexW2565008879

What OpenQuestion holds

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LicenceCC BY-NC
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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.