Cellular Organization of the Subventricular Zone in the Adult Human Brain: A Niche of Neural Stem Cells

Abstract

The dogma that the brain is a quiescent organ incapable of postnatal neuron generation was first challenged in the sixties by Joseph Altman (Altman, 1962). He described the presence of thymidine-labeled cells in the subependymal zone located along the ventricular walls, which suggested the presence of dividing neurons in this brain region (Altman and Gopal, 1965; Altman and Das, 1967). A decade after, these findings were confirmed by other group using electron microscopy analyses (Kaplan and Hinds, 1977). Later, further studies described ongoing neurogenesis in female canaries (Goldman and Nottebohm, 1983), lizards (Perez-Canellas and Garcia-Verdugo, 1996) and the adult mammalian brain (McDermott and Lantos, 1990; McDermott and Lantos, 1991; Lois and Alvarez-Buylla, 1993; Kornack and Rakic, 1995; Huang et al., 1998; Garcia-Verdugo et al., 2002). This process is mainly confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus (Reznikov, 1991; Luskin, 1993; Lois and Alvarez-Buylla, 1994). The SVZ is the largest neurogenic niche in the adult brain (Luskin, 1993; AlvarezBuylla and Garcia-Verdugo, 2002). Within this region resides a subpopulation of astrocytes with stem-cell-like features (Doetsch et al., 1999; Laywell et al., 2000; Imura et al., 2003; Morshead et al., 2003; Garcia et al., 2004). Recently, it has been suggested that the SVZ may be not only a source of neural precursor for brain repair, but also a source of brain tumors (Ignatova et al., 2002; Galli et al., 2004; Sanai et al., 2005; Vescovi et al., 2006). These hypotheses highlight the importance of studying and understanding the organization and regulation of the SVZ precursors. This chapter discusses and analyzes the cytoarchitecture and cellular composition of the human SVZ, as well as, its potential implications on the clinical treatment of neurodegenerative diseases and brain tumors.