, 2008) such that viral labeling and expression methods, of the sort used by Carlén et al., would not only have access to ependymal cells, but also to at least some SVZ stem cells. Those caveats aside, the work of Carlén and colleagues nevertheless raises some interesting questions about the impact of Notch signaling on cellular proliferation and the maintenance of specific neural cell types. A recent study in the adult zebrafish brain (Chapouton et al., 2010) has interesting similarities with several of the rodent studies
described above, regarding (1) the role of Notch in stem cell quiescence (Carlén et al., 2009), (2) the coexistence of both proliferatively active and quiescent NSCs in the dentate gyrus (Lugert et al., 2010), and (3) interactions between intermediate progenitors and NSCs (Aguirre et al., 2010). In the zebrafish brain there are radial glial stem cells that can generate new neurons, and Androgen Receptor Antagonist mw Chapouton et al. found that those radial glia can be either proliferatively active or quiescent and can move back and forth between those states as needed (Chapouton et al., 2010). They argue that the quiescent
state is maintained by Notch signaling, and receptor activation is driven by ligand present on intermediate progenitors. Thus, the more intermediate progenitors there are, the more the system will feed back to activate Notch and inhibit additional NSC divisions. This is similar to the observation made by Carlén et al. in the mouse SVZ that Notch may be required for ependymal cell quiescence (Carlén et al., 2009). selleck inhibitor While some similarities can be noted, the zebrafish study also seems to contradict several mouse studies where Notch receptor or ligand overexpression results in stem cell proliferation and self-renewal rather than quiescence (Aguirre et al.,
2010, Androutsellis-Theotokis et al., 2006, Mizutani et al., 2007 and Yoon et al., 2004). These differences may reveal species-specific phenomena, or may indicate that Notch promotes a cell fate that is quiescent or proliferative, depending upon the availability of other cues. All told, while our understanding of the role of Notch in adult neurogenesis has lagged behind our understanding of it during development, concrete progress Idoxuridine is now underway with numerous studies having emerged recently. Those studies have shown that the fundamentals of Notch signaling during embryonic neurogenesis apply to the germinal zones in the postnatal brain. By studying the well-characterized and highly stereotypical cellular heterogeneity of the postnatal SVZ and SGZ, and how Notch is utilized in distinct subsets of cells, we may uncover novel principles pertinent to Notch regulation in the developing brain as well. A number of studies have examined the role of the Notch pathway in the differentiation of neurons, both during development and postnatally (Berezovska et al., 1999, Breunig et al., 2007, Franklin et al., 1999, Huang et al., 2005, Kurisu et al.