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Article: Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

TitleSox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea
Authors
Issue Date2008
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 47, p. 18395-18401 How to Cite?
AbstractSox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain- and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/58253
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
Funding AgencyGrant Number
Council of Hong KongHKU7385/02M
National Institutes of HealthR01 DC005590
R01 EYO1861
National Institute on Deafness and Other Communication Disorders intramural program
Funding Information:

We thank Drs. A. Kiernan, A. Felling, and T. Friedman for reading the manuscript and C. Woods, CW. Kramer, T. Dennison, and Dr. EC Driver for technical assistance. K.S.E.C. was supported by the Research Grants Council of Hong Kong HKU7385/02M, B.F. by National Institutes of Health Grant R01 DC005590, L.H.P. by National Institutes of Health Grant R01 EYO1861. This work was supported by the National Institute on Deafness and Other Communication Disorders intramural program.

References

 

DC FieldValueLanguage
dc.contributor.authorDabdoub, Aen_HK
dc.contributor.authorPuligilla, Cen_HK
dc.contributor.authorJones, JMen_HK
dc.contributor.authorFritzsch, Ben_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorPevny, LHen_HK
dc.contributor.authorKelley, MWen_HK
dc.date.accessioned2010-05-31T03:26:51Z-
dc.date.available2010-05-31T03:26:51Z-
dc.date.issued2008en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 47, p. 18395-18401en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58253-
dc.description.abstractSox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain- and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea. © 2008 by The National Academy of Sciences of the USA.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCochlea - cytology - growth & developmenten_HK
dc.subject.meshHair Cells, Auditory, Inner - cytologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshReceptors, Notch - metabolismen_HK
dc.subject.meshSOXB1 Transcription Factors - metabolismen_HK
dc.subject.meshSignal Transductionen_HK
dc.titleSox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochleaen_HK
dc.typeArticleen_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.0808175105en_HK
dc.identifier.pmid19011097en_HK
dc.identifier.scopuseid_2-s2.0-57449114544en_HK
dc.identifier.hkuros157180en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57449114544&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume105en_HK
dc.identifier.issue47en_HK
dc.identifier.spage18395en_HK
dc.identifier.epage18401en_HK
dc.identifier.isiWOS:000261489300065-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDabdoub, A=6507497803en_HK
dc.identifier.scopusauthoridPuligilla, C=17135779100en_HK
dc.identifier.scopusauthoridJones, JM=7406480369en_HK
dc.identifier.scopusauthoridFritzsch, B=7006714975en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridPevny, LH=6603355048en_HK
dc.identifier.scopusauthoridKelley, MW=7403230326en_HK

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