Institute for Biology and Molecular Genetics
Thomas Schimmang

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Transcriptional regulators

Functional analysis of transcriptional regulators during auditory development

Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the auditory organ and to control correct patterning of its sensory epithelium, the organ of Corti. We have recently shown 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. 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, we have shown that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian auditory organ.

Recent publications:

  • Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea. Vendrell V, López-Hernández I, Durán Alonso MB, Feijoo-Redondo A, Abello G, Gálvez H, Giráldez F, Lamonerie T, Schimmang T.
    Development. 2015 Aug 15;142(16):2792-800. doi: 10.1242/dev.122465. Epub 2015 Jul 9.

  • N-myc controls proliferation, morphogenesis, and patterning of the inner ear. Domínguez-Frutos E, López-Hernández I, Vendrell V, Neves J, Gallozzi M, Gutsche K, Quintana L, Sharpe J, Knoepfler PS, Eisenman RN, Trumpp A, Giráldez F, Schimmang T.
    J Neurosci. 2011 May 11;31(19):7178-89. doi: 10.1523/JNEUROSCI.0785-11.2011.



 
           
 


Instituto de Biología y Genética Molecular
Universidad de Valladolid - Consejo Superior de Investigaciones CIentíficas
C/ Sanz y Forés s/n
47003 - Valladolid - SPAIN
Phone: (+34) 983-184-818 Fax: (+34) 983-184-800
schimman@ibgm.uva.es

© Thomas Schimmang and www.cytfusion.com