Evidence map›Paper›PMID 22931925›Full record

ArticleThe Journal of investigative dermatology2013

Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3.

Gabriel de la Garza, Jack Robert Schleiffarth, Martine Dunnwald, Anuj Mankad, Jason L Weirather, Gregory Bonde, Stephen Butcher, Tamer A Mansour, Youssef A Kousa, Cindy F Fukazawa and 5 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of investigative dermatology, 2013. 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 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

88 citing papers in PubMed, 131 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. ARHGAP29 promotes keratinocyte proliferation and migration in vitro and is dispensable for in vivo wound healing.Developmental dynamics : an official publication of the American Association of Anatomists · 2025
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Functional analysis ofbioRxiv : the preprint server for biology · 2024
    Article
  17. Neural crest and periderm-specific requirements ofbioRxiv : the preprint server for biology · 2024
    Article
  18. A scATAC-seq atlas of stasis zone in rat skin burn injury wound process.Frontiers in cell and developmental biology · 2024
    Article
  19. Article
  20. Functions of the RIP kinase family members in the skin.Cellular and molecular life sciences : CMLS · 2023
    Review

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Gabriel de la GarzaDepartment of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA, USA.
Jack Robert Schleiffarth
Martine Dunnwald
Anuj Mankad
Jason L Weirather
Gregory Bonde
Stephen Butcher
Tamer A Mansour
Youssef A Kousa
Cindy F Fukazawa
Douglas W Houston
J Robert Manak
Brian C Schutte
Daniel S Wagner
Robert A Cornell
University of Iowa · USMichigan State University · USRice University · US

Funding

Molecular Genetic Epidemiology of Cleft Lip and PalateR37DE008559 · NIDCR · UNIVERSITY OF IOWA · PI MURRAY, JEFFREY C · 2004 to 2013
$6.8M
Research Training Program in OtolaryngologyT32DC000040 · NIDCD · UNIVERSITY OF IOWA · PI HANSEN, MARLAN R · 1993 to 2025
$5.4M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008629 · NIGMS · UNIVERSITY OF IOWA · PI EBERL, DANIEL F · 1997 to 2021
$4.1M
Genomic identification of copy number variants to identify clefting lociR01DE021071 · NIDCR · UNIVERSITY OF IOWA · PI MANAK, JOHN ROBERT · 2010 to 2014
$3.5M
CLONING AND CHARACTERIZATION OF THE VAN DER WOUDE GENER01DE013513 · NIDCR · UNIVERSITY OF IOWA · PI SCHUTTE, BRIAN C · 2000 to 2009
$2.6M
Localized mRNAs in vertebrate axis formationR01GM083999 · NIGMS · UNIVERSITY OF IOWA · PI HOUSTON, DOUGLAS W · 2008 to 2016
$2.6M
Pathways governing survival of neural crest derivativesR01GM067841 · NIGMS · UNIVERSITY OF IOWA · PI CORNELL, ROBERT AARON · 2005 to 2010
$1.4M
Mechanisms of Vertebrate Anterior MorphogenesisR01GM077429 · NIGMS · RICE UNIVERSITY · PI WAGNER, DANIEL S · 2007 to 2011
$1.3M
Bioinformatics Training in the Life Sciences and BiomedicineT32GM082729 · NIGMS · UNIVERSITY OF IOWA · PI CASAVANT, THOMAS L. · 2009 to 2013
$544k
Role of Irf6 in palatal epitheliumF31DE022696 · NIDCR · MICHIGAN STATE UNIVERSITY · PI KOUSA, YOUSSEF A · 2012 to 2013
$60k
NIDCD NIH HHS 5T32DC000040-17NIDCD NIH HHS T32 DC000040NIDCR NIH HHS 1F31DE022696-01NIDCR NIH HHS 5R37DE008559-21NIDCR NIH HHS DE13513NIDCR NIH HHS DE21071NIDCR NIH HHS F31 DE022696NIDCR NIH HHS R01 DE013513NIDCR NIH HHS R01 DE021071NIDCR NIH HHS R37 DE008559NIGMS NIH HHS GM067841NIGMS NIH HHS GM08399904NIGMS NIH HHS R01 GM067841NIGMS NIH HHS R01 GM077429NIGMS NIH HHS R01 GM083999NIGMS NIH HHS R01GM77429NIGMS NIH HHS T32 GM008629NIGMS NIH HHS T32 GM082729
6 · The paper itself

Abstract

IFN regulatory factor 6 (IRF6) is a transcription factor that, in mammals, is required for the differentiation of skin, breast epithelium, and oral epithelium. However, the transcriptional targets that mediate these effects are currently unknown. In zebrafish and frog embryos, Irf6 is necessary for differentiation of the embryonic superficial epithelium, or periderm. Here we use microarrays to identify genes that are expressed in the zebrafish periderm and whose expression is inhibited by a dominant-negative variant of Irf6 (dnIrf6). These methods identify Grainyhead-like 3 (Grhl3), an ancient regulator of the epidermal permeability barrier, as acting downstream of Irf6. In human keratinocytes, IRF6 binds conserved elements near the GRHL3 [corrected] promoter. We show that one of these elements has enhancer activity in human keratinocytes and zebrafish periderm, suggesting that Irf6 directly stimulates Grhl3 expression in these tissues. Simultaneous inhibition of grhl1 and grhl3 disrupts periderm differentiation in zebrafish, and, intriguingly, forced grhl3 expression restores periderm markers in both zebrafish injected with dnIrf6 and frog embryos depleted of Irf6. Finally, in Irf6-deficient mouse embryos, Grhl3 expression in the periderm and oral epithelium is virtually absent. These results indicate that Grhl3 is a key effector of Irf6 in periderm differentiation.

Indexed as

AnimalsDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalGene SilencingGerm LayersHumansInterferon Regulatory FactorsKeratinocytesMicePromoter Regions, GeneticTranscription FactorsZebrafishZebrafish ProteinsDNA-Binding ProteinsGrhl1 protein, zebrafishGRHL3 protein, humanGrhl3 protein, mouseGRHL3 protein, zebrafishInterferon Regulatory FactorsIRF6 protein, humanIRF6 protein, zebrafishTranscription FactorsZebrafish Proteins

Identifiers

PMID22931925
PMCPMC3541433
OpenAlexW2028689768

What OpenQuestion holds

Textmetadata
LicenceTDM
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.