ROLE OF P63 IN THE PATHOGENESIS OF THE AEC SYNDROME: IN VITRO AND IN VIVO MODELS

Human AEC, EEC and SHFM syndromes are characterized by hands and feet malformations, cleft palate, alterations in glands and in the skin. They are caused by mutations in a single gene -p63-which codes for a protein that regulates gene expression, inhibiting or activaing specific genes. In particular, transcription is regulated by a complex set of events, involving the interactions of transcription factors with DNA and with coactivators and/or corepressor proteins. Little is known about the genes activated/repressed by p63 and about the interactions with other proteins. The goal of our Project is to identify genes that are targeted by p63 and proteins that specifically interact with a discrete part of p63, the SAM domain, which has an inhibitory function and which is mutated in the patients with the AEC syndrome. Moreover, we plan to develop a mouse model for AEC in which one could study in detail the pathogenensis of this desease.