Chondroitin sulfate/dermatan sulfate (CS/DS) proteoglycans, major components of the central nervous system, have the potential to interact with a wide range of growth factors and neurotrophic factors that influence neuronal migration, axon guidance pathways, and neurite outgrowth. Recent studies have also revealed the role of CS/DS chains in the orchestration of the neural stem/progenitor cell micromilieu. Individual functional proteins recognize a set of multiple overlapping oligosaccharide sequences decorated to give different sulfation patterns, which are termed here "wobble CS/DS oligosaccharide motifs," and induce signaling pathways essential for the proliferation, selfrenewal, and cell lineage commitment of neural stem/progenitor cells.The discovery of populations of multipotent self-renewing neural stem cells within fetal and adult brains has raised the hope of developing new therapeutic strategies for CNS disorders. Neural stem/progenitor cells (NSPCs) 3 are defined as self-renewing multipotential cells that can generate all types of neural cells, including neurons and glia (astrocytes and oligodendrocytes). In an adult brain, NSPCs are present in two distinct regions: in the subgranular zone of the dentate gyrus of the hippocampus and in the subventricular zone (SVZ) of the lateral ventricles (1-4). During brain development, the neuroepithelial cells of the neural tube expand and self-renew by symmetric division. With increasing thickness of the neuroectoderm, radial glial cells emerge and fulfill the role of neural stem cells. In the first wave, these cells self-renew by symmetrical divisions. In parallel, an asymmetric division pattern develops in which each division cycle gives rise to a radial glial cell and a neuronal progenitor. This phase of neurogenesis is followed by a phase of gliogenesis. In many regions of the CNS, oligodendrocytes precede the formation of astrocytes, which constitute the final population that is formed in the developing CNS (5). The radial glial cells can transform into astrocytes, and the subpopulation of astrocytes in the SVZ has been identified as NSPCs in the adult brain (6). Thereafter, the radial glia recede. Adult forms of radial glia are preserved as Bergmann glia and Müller glia solely in the cerebellum and retina, respectively (7, 8). Thus, NSPCs, which are characterized by their high proliferative potential while retaining self-renewal and pluripotency, encompass neuroepithelial cells, radial glial cells, and SVZ astrocytes (9, 10). The self-renewal and differentiation properties of NSPCs are modulated by intrinsic factors such as transcription factors, intercellular interactions, and extrinsic factors present in the extracellular matrix (ECM). Understanding how these factors regulate the differentiation of NSPCs is essential to exploit potential therapeutic applications to treating various neurodegenerative disorders and spinal cord injuries.
Neural Stem Cell NicheThe microenvironment where the NSPCs reside and maintain their self-renewal, proliferation, and d...
