title: OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Ramona
authors.initials: R
authors.lastname: Palombo
authors.affiliation: Department of Experimental and Clinical Medicine, Università dell'Insubria, via Dunant 5, 21100 Varese, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Porta
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bruno
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Serra
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Karthik
authors.initials: K
authors.lastname: Neduri
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Viziano
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Alessandrini
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Micarelli
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ottaviani
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133 Rome, Italy.|Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.affiliation: Biochemistry Laboratory, IDI-IRCCS-FLMM, c/o Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Terrinoni
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003051:Cochlea / Q000196:embryology*; D004476:Ectodermal Dysplasia / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008266:Macula Lutea / Q000196:embryology*; D051379:Mice; D051857:Otx Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014722:Vestibule, Labyrinth / Q000502:physiology
chemical_list: C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Cochlea; Ectodermal Dysplasia; Macula; OTX2; TAp63