N-myc controls proliferation, morphogenesis, and patterning of the inner ear

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• dc.contributor.author Domínguez Frutos, Elenaca
• dc.contributor.author López Hernández, Irisca
• dc.contributor.author Vendrell, Víctorca
• dc.contributor.author Neves, Joanaca
• dc.contributor.author Gallozzi, Micaelaca
• dc.contributor.author Gutsche, Katjaca
• dc.contributor.author Quintana, Lauraca
• dc.contributor.author Sharpe, Jamesca
• dc.contributor.author Knoepfler, Paul S.ca
• dc.contributor.author Eisenman, Robert N.ca
• dc.contributor.author Trumpp, Andreasca
• dc.contributor.author Giráldez, Fernandoca
• dc.contributor.author Schimmang, Thomasca
• dc.date.accessioned 2012-07-05T06:53:31Z
• dc.date.available 2012-07-05T06:53:31Z
• dc.date.issued 2011ca
• dc.description.abstract Myc family members play crucial roles in regulating cell proliferation, size, and differentiation during organogenesis. Both N-myc and c-myc are expressed throughout inner ear development. To address their function in the mouse inner ear, we generated mice with conditional deletions in either N-myc or c-myc. Loss of c-myc in the inner ear causes no apparent defects, whereas inactivation of N-myc results in reduced growth caused by a lack of proliferation. Reciprocally, the misexpression of N-myc in the inner ear increases proliferation. Morphogenesis of the inner ear in N-myc mouse mutants is severely disturbed, including loss of the lateral canal, fusion of the cochlea with the sacculus and utriculus, and stunted outgrowth of the cochlea. Mutant cochleas are characterized by an increased number of cells exiting the cell cycle that express the cyclin-dependent kinase inhibitor p27Kip1 and lack cyclin D1, both of which control the postmitotic state of hair cells. Analysis of different molecular markers in N-myc mutant ears reveals the development of a rudimentary organ of Corti containing hair cells and the underlying supporting cells. Differentiated cells, however, fail to form the highly ordered structure characteristic for the organ of Corti but appear as rows or clusters with an excess number of hair cells. The Kölliker's organ, a transient structure neighboring the organ of Corti and a potential source of ectopic hair cells, is absent in the mutant ears. Collectively, our data suggest that N-myc regulates growth, morphogenesis, and pattern formation during the development of the inner ear.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Domínguez-Frutos E, López-Hernández I, Vendrell V, Neves J, Gallozzi M, Gutsche K et al. N-myc controls proliferation, morphogenesis, and patterning of the inner ear. J Neurosci. 2011;31(19):7178-89. DOI: 10.1523/​JNEUROSCI.0785-11.2011ca
• dc.identifier.doi http://dx.doi.org/10.1523/JNEUROSCI.0785-11.2011
• dc.identifier.issn 0270-6474ca
• dc.identifier.uri http://hdl.handle.net/10230/16653
• dc.language.iso engca
• dc.publisher Society for Neuroscienceca
• dc.relation.ispartof Journal of Neuroscience. 2011;31(19):7178-89
• dc.rights © 2011, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/31/19/7178.longca
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Trastorns auditius -- Aspectes genètics
• dc.subject.other Genètica evolutiva
• dc.title N-myc controls proliferation, morphogenesis, and patterning of the inner earca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersion