Journal article
Role of p63 and the Notch pathway in cochlea development and sensorineural deafness
A Terrinoni, V Serra, E Bruno, A Strasser, E Valente, ER Flores, H Van Bokhoven, X Lu, RA Knight, G Melino
Proceedings of the National Academy of Sciences of the United States of America | Published : 2013
Abstract
The ectodermal dysplasias are a group of inherited autosomal dominant syndromes associated with heterozygous mutations in the Tumor Protein p63 (TRP63) gene. Here we show that, in addition to their epidermal pathology, a proportion of these patients have distinct levels of deafness. Accordingly, p63 null mouse embryos showmarked cochlea abnormalities, and the transactivating isoform of p63 (TAp63) protein is normally found in the organ of Corti. TAp63 transactivates hairy and enhancer of split 5 (Hes5) and atonal homolog 1 (Atoh1), components of the Notch pathway, known to be involved in cochlear neuroepithelial development. Strikingly, p63 null mice show morphological defects of the organ o..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank Dr. Eleonora Candi for constructive comments, Mr. M. Cook for help with harvesting embryos, and Drs. A. Villunger, C. L. Scott, and J. M. Adams for gifts of mice. This work was supported by the Medical Research Council, United Kingdom; MIUR/PRIN (20078P7T3K_001)/FIRB (RBIP06LCA9_0023, RBIP06LCA9_0C), AIRC (2008-2010_33-08) (#5471) (2011-IG11955), Associazione Italiana Ricerca sul Cancro (AIRC) 5xmille (#9979), Ministero dell'Istruzione e Ricerca Scientifica (MIUR)/Progetti di Ricerca di Interesse Nazionale (PRIN) 2008MRLSNZ_004, and Telethon Grant GGPO9133 (to G.M.); National Health and Medical Research Council of Australia Program Grant 461221, Australia Fellowship; and Leukemia and Lymphoma Society Specialized Center of Research (SCOR) Grant 7413. Research described in this article was also supported in part by Min. Salute (Ricerca oncologica 26/07) Istituto Dermopatico dell'Immacolata (RF06 c. 73, RF07 c. 57, RF08 c. 15, RF07 c. 57) (to G. M.) and Independent Research Institutes Infrastructure Support Scheme (IRISS) grants through the Australian Government and the Victorian State Government Operational Infrastructure Support (OIS).