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Article: Sox2 as a prosensory and proneural gene in the developing mouse cochlea.

TitleSox2 as a prosensory and proneural gene in the developing mouse cochlea.
Authors
Issue Date2008
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbio
Citation
Developmental Biology, 2008, v. 319 n. 2, p. 535 How to Cite?
AbstractThe mammalian cochlea is comprised of three main components; mechanosensory hair cells, non-sensory cells, and primary afferent neurons all of which are derived from cells within the otocyst. The Sox2 transcription factor is expressed in progenitor cells within the otocyst that become specified as prosensory or proneural. Here, we demonstrate that Sox2 expression becomes downregulated in hair cells as they differentiate due to a mutually antagonistic relationship between Sox2 and Atoh1, a bHLH transcription factor that is necessary for hair cell formation. Overexpression of Sox2 antagonizes hair cell formation, while overexpression of Atoh1 in cells that express Sox2 results in Sox2 downregulation and hair cell formation. In contrast, only 50% of cells co-transfected with Atoh1 and Sox2 develop as hair cells. These results were confirmed in vivo in hypomorphic Sox2EGFP/LP mice which express only 20% of the normal levels of Sox2. By comparison with WT cochleae, early differentiation and overproduction of hair cells are observed in Sox2 hypomorphs due to reduction in the antagonistic levels of Sox2 on Atoh1. In contrast with the biphasic role of Sox2 in sensory cell formation, its role in neuronal development is more direct. The cochlear spiral ganglion consists of bipolar neurons that connect hair cells to the cochlear nucleus. We show that Sox2 is expressed in these neurons and that the spiral ganglion neurons are absent in Sox2 mutants. Moreover, we demonstrate that non-sensory epithelial cells within the developing inner ear can be converted to a neuronal identity through overexpression of Sox2 indicating a role for Sox2 in neurogenesis in the inner ear.
Persistent Identifierhttp://hdl.handle.net/10722/68041
ISSN
2015 Impact Factor: 3.155
2015 SCImago Journal Rankings: 2.554

 

DC FieldValueLanguage
dc.contributor.authorPuligilia, Cen_HK
dc.contributor.authorDabdoub, Aen_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorPevny, LHen_HK
dc.contributor.authorKelley, MW-
dc.date.accessioned2010-09-06T06:00:46Z-
dc.date.available2010-09-06T06:00:46Z-
dc.date.issued2008en_HK
dc.identifier.citationDevelopmental Biology, 2008, v. 319 n. 2, p. 535en_HK
dc.identifier.issn0012-1606en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68041-
dc.description.abstractThe mammalian cochlea is comprised of three main components; mechanosensory hair cells, non-sensory cells, and primary afferent neurons all of which are derived from cells within the otocyst. The Sox2 transcription factor is expressed in progenitor cells within the otocyst that become specified as prosensory or proneural. Here, we demonstrate that Sox2 expression becomes downregulated in hair cells as they differentiate due to a mutually antagonistic relationship between Sox2 and Atoh1, a bHLH transcription factor that is necessary for hair cell formation. Overexpression of Sox2 antagonizes hair cell formation, while overexpression of Atoh1 in cells that express Sox2 results in Sox2 downregulation and hair cell formation. In contrast, only 50% of cells co-transfected with Atoh1 and Sox2 develop as hair cells. These results were confirmed in vivo in hypomorphic Sox2EGFP/LP mice which express only 20% of the normal levels of Sox2. By comparison with WT cochleae, early differentiation and overproduction of hair cells are observed in Sox2 hypomorphs due to reduction in the antagonistic levels of Sox2 on Atoh1. In contrast with the biphasic role of Sox2 in sensory cell formation, its role in neuronal development is more direct. The cochlear spiral ganglion consists of bipolar neurons that connect hair cells to the cochlear nucleus. We show that Sox2 is expressed in these neurons and that the spiral ganglion neurons are absent in Sox2 mutants. Moreover, we demonstrate that non-sensory epithelial cells within the developing inner ear can be converted to a neuronal identity through overexpression of Sox2 indicating a role for Sox2 in neurogenesis in the inner ear.-
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbioen_HK
dc.relation.ispartofDevelopmental Biologyen_HK
dc.titleSox2 as a prosensory and proneural gene in the developing mouse cochlea.en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1606&volume=319 535&spage=&epage=&date=2008&atitle=Sox2+as+a+prosensory+and+proneural+gene+in+the+developing+mouse+cochlea.en_HK
dc.identifier.emailCheah, KSE: hrmbdkc@hkusua.hku.hken_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ydbio.2008.05.249-
dc.identifier.hkuros149451en_HK

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