Notch signaling plays a crucial role in regulating stem cell numbers both in vitro and in vivo. The study shows that activation of the Notch receptor induces the expression of target genes such as Hes3 and Shh through rapid activation of cytoplasmic signals, including Akt, STAT3, and mTOR, thereby promoting the survival of neural stem cells. In both murine somatic and human embryonic stem cells, these positive signals are opposed by a control mechanism involving the p38 mitogen-activated protein kinase. Transient administration of Notch ligands to the brain of adult rats increases the numbers of newly generated precursor cells and improves motor skills after ischaemic injury. The study also demonstrates that Notch ligands, such as Dll4 and Jag1, activate second messenger signaling pathways that support NSC survival in vitro. These ligands induce phosphorylation of Akt and mTOR, which are key regulators of cell growth. Additionally, Notch signaling activates the phosphorylation of STAT3 on Ser 727, which is essential for NSC survival. The results suggest that Notch signaling promotes stem cell survival and differentiation through a pathway that is fundamental to development and cancer. In vivo, Notch ligands were shown to increase the number of BrdU-positive cells in the subventricular zone and improve motor skills in rats with ischaemic injury. These findings indicate that Notch ligands may be used to promote regenerative responses through activation of endogenous cells. The study also highlights the importance of Notch signaling in the regulation of stem cell activity and the potential for developing new transplantation therapies for degenerative diseases. The results suggest that Notch signaling may be a key target for future research in stem cell biology and regenerative medicine.Notch signaling plays a crucial role in regulating stem cell numbers both in vitro and in vivo. The study shows that activation of the Notch receptor induces the expression of target genes such as Hes3 and Shh through rapid activation of cytoplasmic signals, including Akt, STAT3, and mTOR, thereby promoting the survival of neural stem cells. In both murine somatic and human embryonic stem cells, these positive signals are opposed by a control mechanism involving the p38 mitogen-activated protein kinase. Transient administration of Notch ligands to the brain of adult rats increases the numbers of newly generated precursor cells and improves motor skills after ischaemic injury. The study also demonstrates that Notch ligands, such as Dll4 and Jag1, activate second messenger signaling pathways that support NSC survival in vitro. These ligands induce phosphorylation of Akt and mTOR, which are key regulators of cell growth. Additionally, Notch signaling activates the phosphorylation of STAT3 on Ser 727, which is essential for NSC survival. The results suggest that Notch signaling promotes stem cell survival and differentiation through a pathway that is fundamental to development and cancer. In vivo, Notch ligands were shown to increase the number of BrdU-positive cells in the subventricular zone and improve motor skills in rats with ischaemic injury. These findings indicate that Notch ligands may be used to promote regenerative responses through activation of endogenous cells. The study also highlights the importance of Notch signaling in the regulation of stem cell activity and the potential for developing new transplantation therapies for degenerative diseases. The results suggest that Notch signaling may be a key target for future research in stem cell biology and regenerative medicine.