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

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 t...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/25927
Acceso en línea:http://hdl.handle.net/10230/25927
http://dx.doi.org/10.1242/dev.122465
Access Level:acceso abierto
Palabra clave:Còclea
Morfogènesi
Immunohistoquímica
Cochlea
Inner ear
Mouse
Myc
Organ of Corti
Otx
Descripción
Sumario: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.