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Development. 2015 Aug 15;142(16):2792-800. doi: 10.1242/dev.122465. Epub 2015 Jul 9.

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

Author information

1
Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, Valladolid E-47003, Spain.
2
CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Barcelona E-08003, Spain.
3
Institut de Biologie Valrose, University of Nice Sophia Antipolis, UMR UNS/CNRS 7277/INSERM 1091, Nice F-06108, France.
4
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.

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.

KEYWORDS:

Cochlea; Inner ear; Mouse; Myc; Organ of Corti; Otx

PMID:
26160903
DOI:
10.1242/dev.122465
[Indexed for MEDLINE]
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