In addition, the authors provided evidence that NSCs could shift back and forth between proliferative activity and quiescence as needed, and that CBF1 was essential for adult NSC maintenance. In related work, another Dinaciclib group has recently shown that deletion of Notch1 dramatically

reduced the number of NSCs and neurogenesis in the dentate gyrus, but that exercise could counteract this effect specifically by enhancing neuroblast progenitor proliferation (Ables et al., 2010). Although the latter study suggested there was no increase in NSCs, in light of the work of Lugert et al., it is tempting to speculate that an NSC subtype that is responsive to exercise might require CBF1, but not Notch1. Additional work will be needed to determine how the different types of NSCs and other progenitors are uniquely regulated, and what the role of Notch signaling is in that context. Further evidence that neural stem/progenitor signaling heterogeneity exists in the germinal zones of the adult brain has come from use of the TNR mouse line (Mizutani et al., 2007) and detection of endogenous NICD1. One recent study showed that Notch signaling is primarily present in NSCs (type B cells), but not in TAPs (type C cells), in the adult SVZ

(Andreu-Agulló et al., 2009). This finding is consistent with work in the embryonic forebrain showing heterogeneity Selleckchem Y 27632 in the VZ with radial glial NSCs possessing canonical Notch-CBF1 signaling, and INPs having attenuated or redirected signaling (Mizutani et al., 2007). Treatment with the vascular niche factor pigmented

epithelium derived factor (PEDF) could increase Notch signaling, apparently downstream of receptor activation, and instead, at the level of the transcriptional regulatory complex (Andreu-Agulló et al., 2009). The latter was achieved through p65-dependent shuttling of the nuclear corepressor (N-CoR) into the cytoplasm, resulting in derepression of Notch targets. Interestingly, Andreu-Agullo et al. suggested that EGFR is a direct target of Notch-CBF1 signaling, and that PEDF treatment drove symmetric cell division, with high levels of EGFR Tolmetin expression in both daughter cells after NSC divisions. Another recent study has provided evidence for interactions between Notch and EGFR signaling in the postnatal SVZ. That work used a transgenic mouse line to drive expression of the EGFR in type C cells (TAPs), but not the type B cells (NSCs) in that region (Aguirre et al., 2010). Presumably as a result of enhanced EGFR signaling, and subsequent proliferative expansion, that transgenic mouse contains an increased number of type C cells (see Figure 4). Interestingly, those mice also have a reduced number of type B cells, suggesting a potential regulatory interaction between the two cell types.