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The Notch signaling pathway is essential for cell fate decisions and maintaining epigenetic memory during nervous system development. It regulates neural stem cell maintenance, neuronal–glial differentiation, and neural circuit formation. Notch activation, through ligand–receptor interactions, releases the Notch intracellular domain, which modulates gene expression in the nucleus. This context-dependent regulation allows Notch to balance proliferation and differentiation, integrating with other pathways and epigenetic regulators to preserve neural stem cell identity and respond to environmental cues. Notch signaling dysfunction is linked to various neurological disorders, highlighting its critical role in nervous system development and homeostasis. This review explores the multifaceted functions of Notch signaling, emphasizing its impact on cell fate and epigenetic memory in early neurogenesis and the adult brain. • Notch regulates proliferation, differentiation, apoptosis and cell fate from embryogenesis trough adult tissue development. • In the nervous system, Notch sustains stem cells, directs neuronal-glial fate, and orchestrate neural circuits. • Notch shapes neural progenitor identity via epigenetic control, modulating transcription and chromatin remodeling. • Notch effects vary by context, driven by receptor-ligand pairing and crosstalk with other signaling pathways. • Notch support adult neurogenesis and repair; its disruption contributes to neurodegeneration and brain tumor formation.
González et al. (Mon,) studied this question.