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Article: Eya1-Six1 Interaction Is Sufficient to Induce Hair Cell Fate in the Cochlea by Activating Atoh1 Expression in Cooperation with Sox2

TitleEya1-Six1 Interaction Is Sufficient to Induce Hair Cell Fate in the Cochlea by Activating Atoh1 Expression in Cooperation with Sox2
Authors
Issue Date2012
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/devcel
Citation
Developmental Cell, 2012, v. 22 n. 2, p. 377-390 How to Cite?
AbstractInner-ear hair cell differentiation requires Atoh1 function, while Eya1, Six1, and Sox2 are coexpressed in sensory progenitors and mutations in these genes cause sensorineural hearing loss. However, how these genes are linked functionally and the transcriptional networks controlling hair cell induction remain unclear. Here, we show (1) that Eya1/Six1 are necessary for hair cell development, and their coexpression in mouse cochlear explants is sufficient to induce hair cell fate in the nonsensory epithelium expressing low-level Sox2 by activating not only Atoh1-dependent but also Atoh1-independent pathways and (2) that both pathways induce Pou4f3 to promote hair cell differentiation. Sox2 cooperates with Eya1/Six1 to synergistically activate Atoh1 transcription via direct binding to the conserved Sox- and Six-binding sites in Atoh1 enhancers, and these proteins physically interact. Our findings demonstrate that direct and cooperative interactions between the Sox2, Six1, and Eya1 proteins coordinate Atoh1 expression to specify hair cell fate. Atoh1 initiates induction of auditory hair cells in the developing inner ear. Ahmed etal. define transcriptional complexes containing Eya1/Six1 and Sox2 transcription factors as crucial regulators of Atoh1 and Atoh1-independent hair cell formation. Misexpression of these transcription factors induces hair cells de novo. © 2012 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/181184
ISSN
2015 Impact Factor: 9.338
2015 SCImago Journal Rankings: 7.338
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAhmed, Men_US
dc.contributor.authorWong, EYMen_US
dc.contributor.authorSun, Jen_US
dc.contributor.authorXu, Jen_US
dc.contributor.authorWang, Fen_US
dc.contributor.authorXu, PXen_US
dc.date.accessioned2013-02-21T02:02:22Z-
dc.date.available2013-02-21T02:02:22Z-
dc.date.issued2012en_US
dc.identifier.citationDevelopmental Cell, 2012, v. 22 n. 2, p. 377-390en_US
dc.identifier.issn1534-5807en_US
dc.identifier.urihttp://hdl.handle.net/10722/181184-
dc.description.abstractInner-ear hair cell differentiation requires Atoh1 function, while Eya1, Six1, and Sox2 are coexpressed in sensory progenitors and mutations in these genes cause sensorineural hearing loss. However, how these genes are linked functionally and the transcriptional networks controlling hair cell induction remain unclear. Here, we show (1) that Eya1/Six1 are necessary for hair cell development, and their coexpression in mouse cochlear explants is sufficient to induce hair cell fate in the nonsensory epithelium expressing low-level Sox2 by activating not only Atoh1-dependent but also Atoh1-independent pathways and (2) that both pathways induce Pou4f3 to promote hair cell differentiation. Sox2 cooperates with Eya1/Six1 to synergistically activate Atoh1 transcription via direct binding to the conserved Sox- and Six-binding sites in Atoh1 enhancers, and these proteins physically interact. Our findings demonstrate that direct and cooperative interactions between the Sox2, Six1, and Eya1 proteins coordinate Atoh1 expression to specify hair cell fate. Atoh1 initiates induction of auditory hair cells in the developing inner ear. Ahmed etal. define transcriptional complexes containing Eya1/Six1 and Sox2 transcription factors as crucial regulators of Atoh1 and Atoh1-independent hair cell formation. Misexpression of these transcription factors induces hair cells de novo. © 2012 Elsevier Inc.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/devcelen_US
dc.relation.ispartofDevelopmental Cellen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors - Genetics - Metabolismen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshChromatin Immunoprecipitationen_US
dc.subject.meshCochlea - Cytology - Metabolismen_US
dc.subject.meshElectrophoretic Mobility Shift Assayen_US
dc.subject.meshElectroporationen_US
dc.subject.meshEmbryo, Mammalian - Cytology - Metabolismen_US
dc.subject.meshGene Expression Regulation, Developmentalen_US
dc.subject.meshHair Cells, Auditory - Metabolismen_US
dc.subject.meshHomeodomain Proteins - Genetics - Metabolismen_US
dc.subject.meshImmunoenzyme Techniquesen_US
dc.subject.meshImmunoprecipitationen_US
dc.subject.meshIntracellular Signaling Peptides And Proteins - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMutation - Geneticsen_US
dc.subject.meshNuclear Proteins - Genetics - Metabolismen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshProtein Tyrosine Phosphatases - Genetics - Metabolismen_US
dc.subject.meshSoxb1 Transcription Factors - Genetics - Metabolismen_US
dc.titleEya1-Six1 Interaction Is Sufficient to Induce Hair Cell Fate in the Cochlea by Activating Atoh1 Expression in Cooperation with Sox2en_US
dc.typeArticleen_US
dc.identifier.emailWong, EYM: elainewg@hku.hken_US
dc.identifier.authorityWong, EYM=rp01718en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.devcel.2011.12.006en_US
dc.identifier.pmid22340499-
dc.identifier.scopuseid_2-s2.0-84863011620en_US
dc.identifier.hkuros270310-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863011620&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume22en_US
dc.identifier.issue2en_US
dc.identifier.spage377en_US
dc.identifier.epage390en_US
dc.identifier.isiWOS:000300473300016-
dc.publisher.placeUnited Statesen_US
dc.identifier.f100014218959-
dc.identifier.scopusauthoridAhmed, M=55445723800en_US
dc.identifier.scopusauthoridWong, EYM=36719382700en_US
dc.identifier.scopusauthoridSun, J=8964410600en_US
dc.identifier.scopusauthoridXu, J=54986022000en_US
dc.identifier.scopusauthoridWang, F=20836393000en_US
dc.identifier.scopusauthoridXu, PX=7202215527en_US

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