After Notch activation by Delta, intracellular domain of Notch and the mammalian Suppressor of Hairless RBP-J activate Hairy and Enhancer-of-split 1 (Hes1), which leads to suppression of Ngn3 expression. Therefore, it is likely that suppression of the Notch pathway leads to differentiation from pancreatic progenitor cells to Ngn3-positive endocrine cell lineage and that, in contrast, activation of the Notch pathway preserves pancreatic progenitor cells from differentiation to Ngn3-positive endocrine cell lineage.