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Article: Sox2 as a prosensory and proneural gene in the developing mouse cochlea.
Title | Sox2 as a prosensory and proneural gene in the developing mouse cochlea. |
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Authors | |
Issue Date | 2008 |
Publisher | Academic 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/68041 |
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 1.147 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Puligilia, C | en_HK |
dc.contributor.author | Dabdoub, A | en_HK |
dc.contributor.author | Cheah, KSE | en_HK |
dc.contributor.author | Pevny, LH | en_HK |
dc.contributor.author | Kelley, MW | - |
dc.date.accessioned | 2010-09-06T06:00:46Z | - |
dc.date.available | 2010-09-06T06:00:46Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | Developmental Biology, 2008, v. 319 n. 2, p. 535 | en_HK |
dc.identifier.issn | 0012-1606 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/68041 | - |
dc.description.abstract | The 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.language | eng | en_HK |
dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbio | en_HK |
dc.relation.ispartof | Developmental Biology | en_HK |
dc.title | Sox2 as a prosensory and proneural gene in the developing mouse cochlea. | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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.email | Cheah, KSE: hrmbdkc@hkusua.hku.hk | en_HK |
dc.identifier.authority | Cheah, KSE=rp00342 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.ydbio.2008.05.249 | - |
dc.identifier.hkuros | 149451 | en_HK |
dc.identifier.isi | WOS:000257734600257 | - |
dc.identifier.issnl | 0012-1606 | - |