Evidence map›Paper›PMID 23406904›Full record

ArticleDevelopment (Cambridge, England)2013

Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis.

Igor O Nasonkin, Shannath L Merbs, Kevin Lazo, Verity F Oliver, Matthew Brooks, Krushangi Patel, Raymond A Enke, Jacob Nellissery, Milan Jamrich, Yun Z Le and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.6field-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

54 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.International journal of molecular sciences · 2024
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Apical CLC-2 in retinal pigment epithelium is crucial for survival of the outer retina.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  16. Article
  17. Epigenetic regulation of retinal development.Epigenetics & chromatin · 2021
    Review
  18. Article
  19. Article
  20. 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

16 authors at 3 institutions in 1 country.

Igor O Nasonkin1Neurobiology-Neurodegeneration and Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shannath L Merbs
Kevin Lazo
Verity F Oliver
Matthew Brooks
Krushangi Patel
Raymond A Enke
Jacob Nellissery
Milan Jamrich
Yun Z Le
Kapil Bharti
Robert N Fariss
Rivka A Rachel
Donald J Zack
Enrique J Rodriguez-Boulan
Anand Swaroop
Baylor College of Medicine · USNational Eye Institute · USUniversity of Oklahoma Health Sciences Center · US

Funding

Regulation of retinal developmentZIAEY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2025
$71.0M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Developing functional and authenticated RPE tissue from iPS cellsZIAEY000533 · NEI · NATIONAL EYE INSTITUTE · PI BHARTI, KAPIL · 2013 to 2025
$14.4M
RETINA--REVERSED POLARITY IN RPER01EY008538 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RODRIGUEZ-BOULAN, ENRIQUE J · 1991 to 2020
$13.4M
Imaging Core UnitZICEY000459 · NEI · NATIONAL EYE INSTITUTE · PI FARISS, ROBERT · 2009 to 2025
$13.1M
THE ROLE OF COMPLEX 1 IN MITOCHONDRIAL DYSFUNCTION & FREE RADICAL PROD IN TYPE 1P20RR024215 · NCRR · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SHORT, KEVIN R. · 2007 to 2011
$11.7M
Project 5 VEGF Signaling in PhotoreceptorsP20GM104934 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI LE, YUN ZHENG · 2012 to 2016
$10.8M
REGULATION OF RHODOPSIN GENE EXPRESSIONR01EY009769 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZACK, DONALD J. · 1992 to 2014
$8.1M
Study of the RPE barrierR01EY020900 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI LE, YUN ZHENG · 2010 to 2013
$1.4M
Molecular and physiological authentication of iPS cell derived RPEZIAEY000531 · NEI · NATIONAL EYE INSTITUTE · PI BHARTI, KAPIL · 2013 to 2016
$445k
NCRR NIH HHS P20 RR024215NCRR NIH HHS P20RR024215NEI NIH HHS EY009769NEI NIH HHS EY020900NEI NIH HHS EY08538NEI NIH HHS P30 EY001765NEI NIH HHS P30EY001765NEI NIH HHS R01 EY008538NEI NIH HHS R01 EY009769NEI NIH HHS R01 EY020900NIGMS NIH HHS P20 GM104934
6 · The paper itself

Abstract

Dysfunction or death of photoreceptors is the primary cause of vision loss in retinal and macular degenerative diseases. As photoreceptors have an intimate relationship with the retinal pigment epithelium (RPE) for exchange of macromolecules, removal of shed membrane discs and retinoid recycling, an improved understanding of the development of the photoreceptor-RPE complex will allow better design of gene- and cell-based therapies. To explore the epigenetic contribution to retinal development we generated conditional knockout alleles of DNA methyltransferase 1 (Dnmt1) in mice. Conditional Dnmt1 knockdown in early eye development mediated by Rx-Cre did not produce lamination or cell fate defects, except in cones; however, the photoreceptors completely lacked outer segments despite near normal expression of phototransduction and cilia genes. We also identified disruption of RPE morphology and polarization as early as E15.5. Defects in outer segment biogenesis were evident with Dnmt1 exon excision only in RPE, but not when excision was directed exclusively to photoreceptors. We detected a reduction in DNA methylation of LINE1 elements (a measure of global DNA methylation) in developing mutant RPE as compared with neural retina, and of Tuba3a, which exhibited dramatically increased expression in mutant retina. These results demonstrate a unique function of DNMT1-mediated DNA methylation in controlling RPE apicobasal polarity and neural retina differentiation. We also establish a model to study the epigenetic mechanisms and signaling pathways that guide the modulation of photoreceptor outer segment morphogenesis by RPE during retinal development and disease.

Indexed as

AnimalsCell Membrane PermeabilityCell PolarityDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationEmbryo, MammalianGene Expression Regulation, DevelopmentalGene Knockdown TechniquesMiceMice, TransgenicMicroarray AnalysisMorphogenesisOrgan SpecificityRetinal Photoreceptor Cell Outer SegmentRetinal Pigment EpitheliumDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDnmt1 protein, mouse

Identifiers

PMID23406904
PMCPMC3585665
OpenAlexW2084976536

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.