The events leading to acquisition of cell identity and neuronal differentiation in the developing cerebral cortex are largely controlled by a signaling pathway composed by Notch, Numb and Delta. Recently, clathrin-mediated endocytosis has emerged as a major mechanism that controls the strength and direction of Notch signaling. In particular epsin, an interactor of clathrin, plays an important role in Notch signaling by promoting ubiquitin-dependent endocytosis of Notch ligands, which in turn leads to signaling. We propose a set of experiments aimed at clarifying the role of epsin in clathrin-mediated endocytosis. We will investigate how disruption of epsin in vivo, and the subsequent block of Notch signaling affects the pattern of neuronal differentiation in the developing cerebral cortex.