Evidence map›Paper›PMID 25908840›Full record

ArticleThe EMBO journal2015

Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo.

Robert Reinhardt, Lázaro Centanin, Tinatini Tavhelidse, Daigo Inoue, Beate Wittbrodt, Jean-Paul Concordet, Juan Ramón Martinez-Morales, Joachim Wittbrodt

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

41 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
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  6. Article
  7. Review
  8. Mutation ofeLife · 2023
    Article
  9. Article
  10. Article
  11. Retina regeneration: lessons from vertebrates.Oxford open neuroscience · 2022
    Review
  12. Eyes on CHARGE syndrome: Roles of CHD7 in ocular development.Frontiers in cell and developmental biology · 2022
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Review
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 3 institutions in 3 countries.

Robert ReinhardtCentre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany.
Lázaro CentaninCentre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany lazaro.centanin@cos.uni-heidelberg.de jochen.wittbrodt@cos.uni-heidelberg.de.
Tinatini TavhelidseCentre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany.
Daigo InoueCentre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany.
Beate WittbrodtCentre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany.
Jean-Paul ConcordetMuséum National d'Histoire Naturelle, Paris, France.
Juan Ramón Martinez-MoralesCentro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain.
Joachim WittbrodtCentre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany lazaro.centanin@cos.uni-heidelberg.de jochen.wittbrodt@cos.uni-heidelberg.de.
Heidelberg University · DECentro Andaluz de Biología del Desarrollo · ESMuséum national d'Histoire naturelle · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transcriptional networks defining stemness in adult neural stem cells (NSCs) are largely unknown. We used the proximal cis-regulatory element (pCRE) of the retina-specific homeobox gene 2 (rx2) to address such a network. Lineage analysis in the fish retina identified rx2 as marker for multipotent NSCs. rx2-positive cells located in the peripheral ciliary marginal zone behave as stem cells for the neuroretina, or the retinal pigmented epithelium. We identified upstream regulators of rx2 interrogating the rx2 pCRE in a trans-regulation screen and focused on four TFs (Sox2, Tlx, Gli3, and Her9) activating or repressing rx2 expression. We demonstrated direct interaction of the rx2 pCRE with the four factors in vitro and in vivo. By conditional mosaic gain- and loss-of-function analyses, we validated the activity of those factors on regulating rx2 transcription and consequently modulating neuroretinal and RPE stem cell features. This becomes obvious by the rx2-mutant phenotypes that together with the data presented above identify rx2 as a transcriptional hub balancing stemness of neuroretinal and RPE stem cells in the adult fish retina.

Indexed as

Adult Stem CellsAnimalsFish ProteinsGene Expression RegulationHomeodomain ProteinsNeural Stem CellsOryziasRetinaTranscription FactorsFish ProteinsHomeodomain ProteinsTranscription Factorsde‐differentiationgene regulationneural stem cellsretinal stem cellstranscriptional network

Identifiers

PMID25908840
PMCPMC4474531
OpenAlexW1993910987

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.