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OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development
OTX proteins, homologs of the Drosophila orthodenticle (Otd), are important for the morphogenesis of the neuroectoderm, and for the central nervous system formation. OTX1 and OTX2 are important for the cochlea and macula development, indeed when OTX1 is knocked down, these organs undergo development...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694063/ https://www.ncbi.nlm.nih.gov/pubmed/26554466 |
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author | Palombo, Ramona Porta, Giovanni Bruno, Ernesto Provero, Paolo Serra, Valeria Neduri, Karthik Viziano, Andrea Alessandrini, Marco Micarelli, Alessandro Ottaviani, Fabrizio Melino, Gerry Terrinoni, Alessandro |
author_facet | Palombo, Ramona Porta, Giovanni Bruno, Ernesto Provero, Paolo Serra, Valeria Neduri, Karthik Viziano, Andrea Alessandrini, Marco Micarelli, Alessandro Ottaviani, Fabrizio Melino, Gerry Terrinoni, Alessandro |
author_sort | Palombo, Ramona |
collection | PubMed |
description | OTX proteins, homologs of the Drosophila orthodenticle (Otd), are important for the morphogenesis of the neuroectoderm, and for the central nervous system formation. OTX1 and OTX2 are important for the cochlea and macula development, indeed when OTX1 is knocked down, these organs undergo developmental failure. Moreover OTX2 transfection revert this effect in OTX1(−/−) mice. The TA isoform of TP63, involved in Notch regulation pathway, has a critical function in the cochlear neuroepithelium differentiation. TAp63 positively regulates Hes5 and Atoh1 transcription. This pathway has been also demonstrated in p63(−/−) mice, and in patients p63 mutated, affected by Ectodermal Dysplasia (ED, OMIM 129810). These patients are affected by mild sensorineural deafness, most likely related to the mutation in p63 gene impairing the Notch pathway. We demonstrated the role of OTX2 on TAp63 regulation necessary for the correct formation of macular neuroepithelium and we confirmed the impairment of vestibular function caused by p63 mutations. Although the abnormalities found in our patient were still at a subclinical extent, aging could exacerbate this impairment and cause a decrease in quality of life. |
format | Online Article Text |
id | pubmed-4694063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-46940632016-01-07 OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development Palombo, Ramona Porta, Giovanni Bruno, Ernesto Provero, Paolo Serra, Valeria Neduri, Karthik Viziano, Andrea Alessandrini, Marco Micarelli, Alessandro Ottaviani, Fabrizio Melino, Gerry Terrinoni, Alessandro Aging (Albany NY) Research Paper OTX proteins, homologs of the Drosophila orthodenticle (Otd), are important for the morphogenesis of the neuroectoderm, and for the central nervous system formation. OTX1 and OTX2 are important for the cochlea and macula development, indeed when OTX1 is knocked down, these organs undergo developmental failure. Moreover OTX2 transfection revert this effect in OTX1(−/−) mice. The TA isoform of TP63, involved in Notch regulation pathway, has a critical function in the cochlear neuroepithelium differentiation. TAp63 positively regulates Hes5 and Atoh1 transcription. This pathway has been also demonstrated in p63(−/−) mice, and in patients p63 mutated, affected by Ectodermal Dysplasia (ED, OMIM 129810). These patients are affected by mild sensorineural deafness, most likely related to the mutation in p63 gene impairing the Notch pathway. We demonstrated the role of OTX2 on TAp63 regulation necessary for the correct formation of macular neuroepithelium and we confirmed the impairment of vestibular function caused by p63 mutations. Although the abnormalities found in our patient were still at a subclinical extent, aging could exacerbate this impairment and cause a decrease in quality of life. Impact Journals LLC 2015-11-10 /pmc/articles/PMC4694063/ /pubmed/26554466 Text en Copyright: © 2015 Palombo et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Palombo, Ramona Porta, Giovanni Bruno, Ernesto Provero, Paolo Serra, Valeria Neduri, Karthik Viziano, Andrea Alessandrini, Marco Micarelli, Alessandro Ottaviani, Fabrizio Melino, Gerry Terrinoni, Alessandro OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development |
title | OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development |
title_full | OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development |
title_fullStr | OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development |
title_full_unstemmed | OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development |
title_short | OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development |
title_sort | otx2 regulates the expression of tap63 leading to macular and cochlear neuroepithelium development |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694063/ https://www.ncbi.nlm.nih.gov/pubmed/26554466 |
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