Evidence map›Paper›PMID 18678597›Full record

ArticleHuman molecular genetics2008

Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear.

Dan Zou, Christopher Erickson, Eun-Hee Kim, Dongzhu Jin, Bernd Fritzsch, Pin-Xian Xu

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
  2. Clinical and Genetic Features inDiagnostics (Basel, Switzerland) · 2026
    Article
  3. Branchio-oto-renal syndrome: a narrative review.Childhood kidney diseases · 2026
    Review
  4. Genome-wide analysis implicates inner ear development in Ménière's disease.medRxiv : the preprint server for health sciences · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Otic Neurogenesis inFrontiers in neuroanatomy · 2021
    Article
  18. Article
  19. The first case of NSHL by direct impression onIranian journal of basic medical sciences · 2018
    Article
  20. Review

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

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

6 authors at 3 institutions in 1 country.

Dan ZouMcLaughlin Research Institute for Biomedical Sciences, Great Falls, MT 59405, USA.
Christopher Erickson
Eun-Hee Kim
Dongzhu Jin
Bernd Fritzsch
Pin-Xian Xu
Icahn School of Medicine at Mount Sinai · USCreighton University · USMcLaughlin Research Institute · US

Funding

The Role of Eya and its Interacting Gene Six in Mammalian Inner Ear DevelopmentR01DC005824 · NIDCD · MC LAUGHLIN RESEARCH INSTITUTE · PI XU, PIN-XIAN · 2002 to 2011
$4.1M
DISSECTING THE EAR NEUROSENSORY DEVELOPMENT.R01DC005590 · NIDCD · UNIVERSITY OF IOWA · PI FRITZSCH, BERND · 2002 to 2010
$3.3M
NIDCD NIH HHS R01 DC005590NIDCD NIH HHS R01 DC005824
6 · The paper itself

Abstract

Haploinsufficiency of the transcription co-activator EYA1 causes branchio-oto-renal syndrome, congenital birth defects that account for as many as 2% of profoundly deaf children; however, the underlying cause for its dosage requirement and its specific role in sensory cell development of the inner ear are unknown. Here, an allelic series of Eya1 were generated to study the basis of Eya1 dosage requirements for sensory organ development. Our results show different threshold requirements for the level of Eya1 in different regions of the inner ear. Short and disorganized hair cell sterocilia was observed in wild-type/null heterozygous or hypomorphic/hypomorphic homozygous cochleae. Patterning and gene-marker analyses indicate that in Eya1 hypomorphic/null heterozygous mice, a reduction of Eya1 expression to 21% of normal level causes an absence of cochlear and vestibular sensory formation. Eya1 is initially expressed in the progenitors throughout the epithelium of all six sensory regions, and later on during sensory cell differentiation, its expression becomes restricted to the differentiating hair cells. We provide genetic evidence that Eya1 activity, in a concentration-dependent manner, plays a key role in the regulation of genes known to be important for sensory development. Furthermore, we show that Eya1 co-localizes with Sox2 in the sensory progenitors and both proteins physically interact. Together, our results indicate that Eya1 appears to be upstream of very early events during the sensory organ development, hair cell differentiation and inner-ear patterning. These results also provide a molecular mechanism for understanding how hypomorphic levels of EYA1 cause inner-ear defects in humans.

Indexed as

AnimalsBone Morphogenetic Protein 4Cells, CulturedCyclin-Dependent Kinase Inhibitor p27Ear, InnerEpithelial CellsEpitheliumFemaleGene DosageGene Expression Regulation, DevelopmentalGlycosyltransferasesHair Cells, Auditory, InnerHumansIntracellular Signaling Peptides and ProteinsMiceMice, Inbred C3HBone Morphogenetic Protein 4Cyclin-Dependent Kinase Inhibitor p27EYA1 protein, humanEya1 protein, mouseGlycosyltransferasesIntracellular Signaling Peptides and ProteinsLfng protein, mouseNuclear ProteinsOtx Transcription FactorsProtein Tyrosine PhosphatasesSox2 protein, mouseSOXB1 Transcription Factors

Identifiers

PMID18678597
PMCPMC2722896
OpenAlexW2121278418

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.