It has been suggested that a wounding stimulus elsewhere in the brain may create a temporarily permissive environment that resembles the stem cell niche, but the signals involved in this environment are unknown (Buffo et al., PF-2341066 2008). Equally interesting is the suggestion that reactive astrocytes located outside the adult VZ-SVZ may be induced to behave as neural progenitors (Robel et al., 2011). Fourth, the finding that the adult VZ-SVZ is patterned as a spatial mosaic raises questions about the initiation and maintenance of this pattern—principally, at what time in development do individual progenitors become committed to a particular neuronal fate, and what pathways are associated with the

generation of specific types of neurons? Finally, the field awaits the application of the many discoveries in model organisms to DAPT research buy our knowledge of the human VZ-SVZ during development, in the mature brain, and after disease or injury. The majority

of detailed studies of the adult VZ-SVZ niche have been completed in rodents, but therapeutic application of our understanding of neural stem cells will require knowledge of how this germinal niche is structured in the human brain. Comparative studies in mammals have highlighted differences in anatomy and proliferative activity between species (Pérez-Martín et al., 2000, Kornack and Rakic, 2001, Luzzati et al., 2003 and Sawamoto et al., 2011). Although neurospheres can be isolated from adult human VZ-SVZ (Kukekov et al., 1999 and Sanai et al., 2004),

proliferation levels in this region are significantly lower than the rates observed in mouse, and there has been extensive debate over whether chains of migrating neurons are present Bay 11-7085 in the adult human brain (Sanai et al., 2004, Sanai et al., 2007, Quiñones-Hinojosa et al., 2006 and Curtis et al., 2007). Recent studies of the developing fetal brain suggest that more robust neuronal production and migration may occur earlier in the development of this region (Guerrero-Cázares et al., 2011). Determining the capacity of human VZ-SVZ cells to proliferate and generate immature neurons as the brain develops, matures, and ages will be essential to harnessing the potential of these cells for therapeutic ends. In model organisms and humans, understanding how the many structural and molecular elements within this region interact to maintain stem cell self-renewal and neurogenesis will be a fascinating challenge as the field advances. Already, our maturing knowledge of how stem cells and neurogenesis are maintained begins to point the way toward expanding and reprogramming these progenitors for neuronal and glial replacement. The authors thank the members of the Álvarez-Buylla, Lim, Kriegstein, and Rowitch laboratories at UCSF for thought-provoking and informative discussions, and Kenneth X. Probst for preparation of the illustrations. R.A.I.