FOXF2 is required for cochlear development in humans and mice

Basit Öğe Kaydı
dc.authoridBlanton, Susan Halloran/0000-0002-5433-3439
dc.authoridCarlsson, Peter/0000-0001-6535-5927
dc.authoridduman, duygu/0000-0001-7583-0349
dc.authoridGürkan, Hakan/0000-0002-8967-6124
dc.authoridFitoz, Suat/0000-0002-0180-0013
dc.authoridatli, emine ikbal/0000-0001-9003-1449
dc.authoridSineni, Claire/0000-0003-4719-2815
dc.authorwosidDuman, Duygu/AAG-7765-2019
dc.authorwosidDemir, Selma/A-1500-2018
dc.authorwosidErgin, Filiz Basak/JEP-6180-2023
dc.authorwosidTekin, Mustafa/ABG-7627-2020
dc.authorwosidBlanton, Susan Halloran/ABF-1323-2021
dc.authorwosidCarlsson, Peter/B-5551-2008
dc.authorwosidduman, duygu/AAF-8093-2020
dc.contributor.authorBademci, Guney
dc.contributor.authorAbad, Clemer
dc.contributor.authorIncesulu, Armagan
dc.contributor.authorElian, Fahed
dc.contributor.authorReyahi, Azadeh
dc.contributor.authorDiaz-Horta, Oscar
dc.contributor.authorCengiz, Filiz B.
dc.date.accessioned2024-06-12T11:19:12Z
dc.date.available2024-06-12T11:19:12Z
dc.date.issued2019
dc.departmentTrakya Üniversitesien_US
dc.description.abstractMolecular mechanisms governing the development of the human cochlea remain largely unknown. Through genome sequencing, we identified a homozygous FOXF2 variant c.325A>T (p.I109F) in a child with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is not found in public databases or in over 1000 ethnicity-matched control individuals. I109 is a highly conserved residue in the forkhead box (Fox) domain of FOXF2, a member of the Fox protein family of transcription factors that regulate the expression of genes involved in embryogenic development as well as adult life. Our in vitro studies show that the half-life of mutant FOXF2 is reduced compared to that of wild type. Foxf2 is expressed in the cochlea of developing and adult mice. The mouse knockout of Foxf2 shows shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Expressions of Eya1 and Pax3, genes essential for cochlear development, are reduced in the cochleae of Foxf2 knockout mice. We conclude that FOXF2 plays a major role in cochlear development and its dysfunction leads to SNHL and developmental anomalies of the cochlea in humans and mice.en_US
dc.description.sponsorshipNational Institutes of Health [R01DC009645, R01DC012836]; Swedish Medical Research Council; Swedish Cancer Foundation; Microsoft Genomics for Researchen_US
dc.description.sponsorshipNational Institutes of Health (R01DC009645 and R01DC012836 to M.T.); Swedish Medical Research Council (VR-M); Swedish Cancer Foundation (P.C.); and Microsoft Genomics for Research (G.B.).en_US
dc.identifier.doi10.1093/hmg/ddy431
dc.identifier.endpage1297en_US
dc.identifier.issn0964-6906
dc.identifier.issn1460-2083
dc.identifier.issue8en_US
dc.identifier.pmid30561639en_US
dc.identifier.scopus2-s2.0-85064510039en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1286en_US
dc.identifier.urihttps://doi.org/10.1093/hmg/ddy431
dc.identifier.urihttps://hdl.handle.net/20.500.14551/25098
dc.identifier.volume28en_US
dc.identifier.wosWOS:000467482600005en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherOxford Univ Pressen_US
dc.relation.ispartofHuman Molecular Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectInner-Earen_US
dc.subjectConvergent Extensionen_US
dc.subjectForkhead Proteinsen_US
dc.subjectCell-Migrationen_US
dc.subjectCleft-Lipen_US
dc.subjectGeneen_US
dc.subjectMutationsen_US
dc.subjectHearingen_US
dc.subjectClassificationen_US
dc.subjectDeafnessen_US
dc.titleFOXF2 is required for cochlear development in humans and miceen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu