THE PREP1 HOX-COFACTOR. ROLES IN DEVELOPMENT AND DISEASES

Prep1 is an important gene since it regulates the expression of many other genes which are essential for embryonic development. In fact the absence of the Prep1 genes causes embryonic lethality with major defects in blood, bone, eye, pancreas, and heart formation. In this project we will continue to analyze the function of Prep1, in particular in embryonic hematopoiesis by deleting the Prep1 gene (conditional Ko) only in hematopoietic cells: the conditional Ko can also be used to delete Prep1 in any other wanted type of cell. Prep1 maps in the critical region of chromosome 21 (the trisomy of which is responsible for the Down Syndrome, DS). We therefore want to set up a model of DS caused by increasing the copy number of the Prep1 gene (and not the entire chromosome 21) to investigate which part of the DS phenotype is due to Prep1. Finally, we want to analyze at the molecular level some novel mechanisms through which Prep1 exerts its action as this information may also lead to find ways to overcome the effects of its overexpression.