Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea

Vendrell, Víctor; López Hernández, Iris; Durán Alonso, Beatriz; Feijoo Redondo, Ana; Abelló Sumpsi, Gina, 1980-; Gálvez García, Héctor, 1989-; Giráldez, Fernando; Lamonerie, Thomas; Schimmang, Thomas

Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea

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dc.contributor.author Vendrell, Víctorca
dc.contributor.author López Hernández, Irisca
dc.contributor.author Durán Alonso, Beatrizca
dc.contributor.author Feijoo Redondo, Anaca
dc.contributor.author Abelló Sumpsi, Gina, 1980-ca
dc.contributor.author Gálvez García, Héctor, 1989-ca
dc.contributor.author Giráldez, Fernandoca
dc.contributor.author Lamonerie, Thomasca
dc.contributor.author Schimmang, Thomasca
dc.date.accessioned 2016-02-23T13:38:47Z
dc.date.available 2016-08-15T02:00:03Z
dc.date.issued 2015
dc.description.abstract Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the cochlea and to control correct patterning of the organ of Corti. We show here that the Otx2 gene, a mammalian ortholog of the Drosophila orthodenticle homeobox gene, is a crucial target of N-myc during inner ear development. Otx2 expression is lost in N-myc mouse mutants, and N-myc misexpression in the chick inner ear leads to ectopic expression of Otx2. Furthermore, Otx2 enhancer activity is increased by N-myc misexpression, indicating that N-myc may directly regulate Otx2. Inactivation of Otx2 in the mouse inner ear leads to ectopic expression of prosensory markers in non-sensory regions of the cochlear duct. Upon further differentiation, these domains give rise to an ectopic organ of Corti, together with the re-specification of non-sensory areas into sensory epithelia, and the loss of Reissner's membrane. Therefore, the Otx2-positive domain of the cochlear duct shows a striking competence to develop into a mirror-image copy of the organ of Corti. Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea.ca
dc.description.sponsorship This work was supported by the Spanish MinEco [BFU2010-15477, BFU2011-24057, BFU2013-40944]; Fundació La Marató de TV3; TerCel [RD06/0010/0000]; and Red de Terapia Célular de la Junta de Castilla y León.
dc.format.mimetype application/pdfca
dc.identifier.citation Vendrell V, López-Hernández I, Durán Alonso MB, Feijoo-Redondo A, Abello G, Gálvez H et al. Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea. Development. 2015;142(16):2792-800. DOI: 10.1242/dev.122465ca
dc.identifier.doi http://dx.doi.org/10.1242/dev.122465
dc.identifier.issn 0927-6467
dc.identifier.uri http://hdl.handle.net/10230/25927
dc.language.iso engca
dc.publisher Company of Biologistsca
dc.relation.ispartof Development. 2015;142(16):2792-800
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-24057
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-40944
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-15477
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.keyword Cochlea
dc.subject.keyword Inner ear
dc.subject.keyword Mouse
dc.subject.keyword Myc
dc.subject.keyword Organ of Corti
dc.subject.keyword Otx
dc.subject.other Còcleaca
dc.subject.other Morfogènesica
dc.subject.other Immunohistoquímicaca
dc.title Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochleaca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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