6. Molecular mechanisms of neural stem cells differentiation

Stem cells persist in specialized niches in discrete regions of the central nervous system, which supports their self-renewal and differentiation throughout the life span. The subgranular zone (SGZ) of the dentate gyrus in the hippocampus and the subventricular zone (SVZ) of the lateral ventricles contain neural stem cells (NSCs) and act as NSC niches in the adult brain. In the SGZ niche, NSCs, as multilineage cells, differentiate into interneurons that finally generate the neurons and astrocytes. Moreover, NSCs of the SVZ niche are capable of generating neurons, oligodendrocytes, and astrocytes. Thus, active neurogenesis continues throughout their life in the mammals, including humans. Emerging findings have shown that intrinsic and extrinsic regulators play a crucial role in NSC differentiation and fate determination. Gene expression, epigenetic remodeling of genes, and various gene boxes such as HOX and SOX genes regulate neurogenesis and differentiation of NSCs. Additionally, several signaling pathways, including JAK/STAT, Notch, MAP Kinases, and Wnt, assist in the development of this trend. Furthermore, different signaling molecules and proteins such as transforming growth factor-beta, bone morphogenetic proteins, or Smad control the progression of this process. Metabolic changes and physiological, pathological, and pharmacological stimuli can also affect neurogenesis in the adult brain. This chapter focuses on the special conditions and molecular mechanisms that direct neural differentiation and specify the ultimate fate of NSCs.