title: Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea.
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.
authors.affiliation: Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, Valladolid E-47003, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Vendrell
authors.affiliation: Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, Valladolid E-47003, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: López-Hernández
authors.affiliation: Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, Valladolid E-47003, Spain.
authors.forename: María Beatriz
authors.initials: MB
authors.lastname: Durán Alonso
authors.affiliation: Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, Valladolid E-47003, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Feijoo-Redondo
authors.affiliation: CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Barcelona E-08003, Spain.
authors.forename: Gina
authors.initials: G
authors.lastname: Abello
authors.affiliation: CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Barcelona E-08003, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Gálvez
authors.affiliation: CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Barcelona E-08003, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Giráldez
authors.affiliation: Institut de Biologie Valrose, University of Nice Sophia Antipolis, UMR UNS/CNRS 7277/INSERM 1091, Nice F-06108, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lamonerie
authors.affiliation: Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, Valladolid E-47003, Spain schimman@ibgm.uva.es.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimmang
mesh_terms: D000818:Animals; D003051:Cochlea / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006309:Hearing / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D051857:Otx Transcription Factors / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
chemical_list: D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D016271:Proto-Oncogene Proteins c-myc
keywords: Cochlea; Inner ear; Mouse; Myc; Organ of Corti; Otx