REGULATION OF THE HEDGEHOG SIGNALING IN NEURAL DEVELOPMENT AND DISEASE: CHARACTERIZATION OF THE ROLE OF REN, A NOVEL SUPPRESSOR OF GLI FUNCTION

Holoprosencephaly is a genetic disease characterized by incomplete cleavage of the brain during embryogenesis and is caused by genetic defects in members of the Hedgehog pathway, which are also responsible of a number of additional inherited diseases due to aberrant development of the nervous and other tissues (Grieg Cephalopolysyndactyly, Pallister-Hall syndrome, Postaxial Polydactyly and VACTERIL), including brain tumors (Gorlin syndrome). However, there remain many gaps in understanding Hedgehog functions and its association with diseases. Filling this gaps appears critically important for the elucidation of pathogenetic issues and for the identification of potential therapeutical targets. We have recently identified a novel gene (REN) that controls neural cell development and is a new regulator of the Hedgehog functions. This proposal plans to study whether this novel gene may represent a target for therapeutical intervention and may play a role in diseases caused by genetic defects of Hedgehog.