• embryonic development
• Huntingtin
• Huntingtina
• neurulation
• neurulazione
• sviluppo embrionale

Huntingtin (Htt) appearance dated back to 800 million years before protostomes/deuterostomes divergence, since its presence in the the slime mold Dictyostelium discoideum has been recently confirmed.One of the main features of Htt is represented by the polyQ tract in its NH2-terminal region. PolyQ stretch appeared in Htt of sea urchin and expands gradually along deuterostomes evolution becoming polymorphic in the highest species of the phylogenetic tree, the Homo sapiens (in which CAG repeats vary from 6 to 35). It has been recently demonstrated that Htt acquires a new function important for neurulation during evolution, in particular in the evolutionary step between Echinodermata and Chordata, where the polyQ tract consolidates at the 18th aminoacidic position. This thesis work is focused at the definition of the Htt domain involved in neurulation. Our experimental approach consisted in complementation assays with truncated portion of Htt performed in mouse embryonic stem (mES) cells, then subjected to neural differentiation protocol (mimicking neurulation in vitro). By using this approach, we discovered that the pro-neurulation function of Htt is embedded in the first 24 aminoacids (including the first 17 aminoacids and the polyQ tract) providing new insights into the evolution of the protein and its activity.