ROLE OF PITX2 GENE, MUTATED IN THE HUMAN RIEGER SYNDROME, IN CELL PROLIFERATION AND MIGRATION DURING MAMMALIAN ORGANOGENESIS

Pitx genes play multiple important functions during mammalian development. These genes are copied in mRNA (transcription), mRNA is translated in proteins and these proteins provide the information required for regulated transcription of other genes. Mice in which Pitx 2 is deleted die before birth displaying severe cardiovascular, pulmonary, ocular, and muscular malformations. Furthermore, the embryos are affected by severe developmental defects of pituitary, mandible, and teeth. The Axelfeld-Rieger syndrome (in which the Pitx 2 gene is mutated) is mainly characterized by craniofacial, ocular (severe and early-onset glaucoma), teeth, and stump defects. Moreover, these patients display growth retardation and cardiovascular malformations. We will study in detail Pitx2 gene function trying to discover the genes whose expression it regulates. We will also try to discover other proteins interacting and cooperating with Pitx2 factor. These studies will allow us to understand the molecular pathogenesis of the Axelfeld-Rieger syndrome.