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

• Published in: Development (Cambridge) Vol. 142; no. 16; pp. 2792 - 2800
• Main Authors: Vendrell, Victor, López-Hernández, Iris, Alonso, María Beatriz Durán, Feijoo-Redondo, Ana, Abello, Gina, Gálvez, Héctor, Giráldez, Fernando, Lamonerie, Thomas, Schimmang, Thomas
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 15.08.2015
• Subjects: Animals; Cochlea; Cochlea - embryology; Cochlea - metabolism; Còclea; Development Biology; Drosophila; Gene Expression Regulation, Developmental; Gene Expression Regulation, Developmental - physiology; Hearing; Hearing - physiology; Immunohistochemistry; Immunohistoquímica; In Situ Hybridization; Inner ear; Life Sciences; Mice; Mice, Transgenic; Morfogènesi; Morphogenesis; Morphogenesis - physiology; Mouse; Myc; Organ of Corti; Otx; Otx Transcription Factors; Otx Transcription Factors - metabolism; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-myc - metabolism; Cochlea; Otx; Mouse; Organ of Corti; Myc; Inner ear
• DOI: 10.1242/dev.122465
• ISSN: 0950-1991; 0927-6467

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 orthologue 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, the work shows that Otx2 acts downstream N-myc and is essential for patterning and the spatial restriction of the sensory domain of the mammalian cochlea.