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

Welcome to the UPF Digital Repository

Domínguez-Frutos E, López-Hernández I, Vendrell V, Neves J, Gallozzi M, Gutsche K, Quintana L, Sharpe J, Knoepfler PS, Eisenman RN, Trumpp A, Giráldez F, Schimmang T. N-myc controls proliferation, morphogenesis, and patterning of the inner ear. J Neurosci. 2011; 31(19): 7178-89. DOI: 10.1523/​JNEUROSCI.0785-11.2011
http://hdl.handle.net/10230/16653
To cite or link this document: http://hdl.handle.net/10230/16653
dc.contributor.author Domínguez Frutos, Elena
dc.contributor.author López Hernández, Iris
dc.contributor.author Vendrell, Víctor
dc.contributor.author Neves, Joana
dc.contributor.author Gallozzi, Micaela
dc.contributor.author Gutsche, Katja
dc.contributor.author Quintana, Laura
dc.contributor.author Sharpe, James
dc.contributor.author Knoepfler, Paul S.
dc.contributor.author Eisenman, Robert N.
dc.contributor.author Trumpp, Andreas
dc.contributor.author Giráldez, Fernando
dc.contributor.author Schimmang, Thomas
dc.date.accessioned 2012-07-05T06:53:31Z
dc.date.available 2012-07-05T06:53:31Z
dc.date.issued 2011
dc.identifier.citation Domínguez-Frutos E, López-Hernández I, Vendrell V, Neves J, Gallozzi M, Gutsche K, Quintana L, Sharpe J, Knoepfler PS, Eisenman RN, Trumpp A, Giráldez F, Schimmang T. N-myc controls proliferation, morphogenesis, and patterning of the inner ear. J Neurosci. 2011; 31(19): 7178-89. DOI: 10.1523/​JNEUROSCI.0785-11.2011
dc.identifier.issn 0270-6474
dc.identifier.uri http://hdl.handle.net/10230/16653
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.language.iso eng
dc.publisher Society for Neuroscience
dc.relation.ispartof J Neurosci. 2011; 31(19): 7178-89
dc.rights (c) 2011, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/31/19/7178.long
dc.subject.other Trastorns auditius -- Aspectes genètics
dc.subject.other Genètica evolutiva
dc.title N-myc controls proliferation, morphogenesis, and patterning of the inner ear
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1523/JNEUROSCI.0785-11.2011
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


See full text

Search


Advanced Search

Browse

My Account

Statistics