Title:
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Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea
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Author:
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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
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Abstract:
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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. |
Abstract:
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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. |
Subject(s):
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-Còclea -Morfogènesi -Immunohistoquímica -Cochlea -Inner ear -Mouse -Myc -Organ of Corti -Otx |
Rights:
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© Company of Biologists http://dev.biologists.org/content/develop/142/16/2792.full.pdf DOI 10.1242/dev.122465 |
Document type:
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Article Article - Published version |
Published by:
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Company of Biologists
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