MAIN LINES OF RESEARCHA first line of research was focused on the role of centromere, a key element of eukaryotic chromosome, in the regulation of cell division under physiological and pathological conditions. In particular, the study demonstrated that the protein CENP-C is a crucial structural component of the centromere that regulates the correct chromosome segregation during cell division. This knowledge may help understand mechanisms underlying proliferation defects under pathological conditions.A second line of research is focusing on understanding the mechanisms underlying two neurodevelopmental disoders: Down Syndrome (DS) and the CDKL5 variant of Rett's syndrome. The ultimate goal of this research is to devise possible therapeutic strategies to ameliorate the severe cognitive disability that characterizes these pathologies. Using a transgenic mouse model for DS (the Ts65Dn mouse), we dissected important molecular mechanisms underlying defective neuron formation and connectivity alterations in DS. By using in vivo and in vitro approaches we identified numerous alterations in the physiology of the trisomic brain. In an attempt to find effective treatments, possibly useful in humans, we are testing therapeutic approaches in order to enhance neuron production and cognitive performance in the Ts65Dn mouse model of DS. The CDKL5 variant of Rett's syndrome is a rare neurodevelopmental disorders due to mutation in the CDKL5 gene. We recently identified physiological cellular targets of CDKL5 and characterized a newly-generated CDKL5 loss-of-function mouse model with a special emphasis on those neuronal alterations that may derive from altered activity of CDKL5 cellular targets. We are testing different therapeutic approaches in order to improve developmental defects and cognitive deficits in the CDKL5 KO mouse model.