FUNCTION OF p63 IN NORMAL SKIN AND IN ECTODERMAL DYSPLASIA SYNDROMES

  • 3 Years 2009/2012
  • 223.000€ Total Award
Ectodermal dysplasia (ED) syndromes are autosomal dominant diseases characterized by developmental craniofacial abnormalities. They are caused by mutations in the p53 homologue gene, p63. For instance, mutations in the p63 gene have been found in patients affected by Ectrodactyly, Ectodermal dysplasia and Cleft lip/palate (EEC) and Ankyloblepharon-Ectodermal Dysplasia-Clefting (AEC) syndromes. p63 is highly expressed in the basal layer of the epidermis and in the apical ectodermal ridge, an epithelium essential for limb morphogenesis. Characterisation of the phenotype of the p63 deficient mouse and the above mentioned syndromes have demonstrated that p63 acts as a transcriptional regulator required for limb formation and craniofacial and epithelial development during embryogenesis. The molecular mechanisms by which p63 controls differentiation and death programs in keratinocytes are still poorly elucidated. Hence, the present project aims to investigate the molecular mechanisms regulating p63 and the role of p63 in skin differentiation and in the pathogenesis of the ED syndromes. To summarize, this project has the following specific aims: 1. Identification and characterization of p63 mutations from ED patients. Analysis of the genes transcriptionally regulated by wt and p63 mutants. 2. Regulation of wild type and mutants p63 steady-state level both by E3 ligases and microRNAs. 3. Generation of mouse disease models for studying the role of p63 in ED diseases in vivo and for the assessment of novel pathways discovered during this project.

Scientific Publications

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