Un approccio genetico al ruolo e meccanismo d'azione del fattore trascrizionale SOX2 nelle cellule staminali neurali : delezione condizionale di SOX2 nel topo

In the mouse nervous system, Sox2 is expressed in stem cells and early precursors, and in few mature neurons (Zappone et al., 2000; Ferri et al., 2004). Adult Sox2-deficient mice, in which Sox2 expression is decreased by about 70%, exhibit neural stem/precursor cell proliferative defects in the hippocampus and periventricular zone (Ferri et al., 2004). I performed in vitro differentiation studies on neurosphere derived neural cells. Neural stem cells from Sox2-deficient mice produce reduced numbers of neural progenitors. Moreover, I found the SOX2 is important for the neural progenitors cell cycle progression. I demonstrated that SOX2 promoted the proliferation of neural stem cells through facilitating the G1/S transition with the levels of cyclin D1 and cyclin E expression in neural progenitors samples. Mash1 is an important regulator of neurogenesis in the ventral telencephalon, where it is required both to specify neuronal precursors and to control the timing of their production. Mash1 is required for the generation of neocortical neurons with characteristics of GABAergic interneurons. Moreover, in vivo Sox2 deficiency causes a reduction of GABAergic neurons (Cavallaro M. et al., 2008). These observations point to a possible role for SOX2 togheter with Mash1 in the genesis of neural progenitors of GABAergic neurons. The early neural progenitors, derive from Sox2-deficient mice produce reduced numbers of MASH1 positive cells. In vivo Chromatin immunoprecipitation assays reveal interactions of SOX2 and Mash1 in early neural progenitor cells. My data also suggest that the specific recruitment of these protein to the Mash1 in the ventral telencephalon defines the spatiotemporal activity of MASH1 in the developing nervous system.