The former would be expected to permit trans signaling with neighboring cells, while the latter, to block signaling find more on a cell-autonomous level through cis interactions between ligand and receptor. All told, these studies are thought provoking and add an interesting new twist to the relevance of apical-basal polarity in neuroepithelial progenitors. Although others have found
such polarity with respect to molecules intrinsic to those cells (Bultje et al., 2009, Chenn and McConnell, 1995, Chenn et al., 1998 and Rasin et al., 2007), this work suggests that asymmetric distribution of cues across the germinal zone also plays a role. Whether a gradient of Notch activity will prove to be a general property DAPT price of neuroepithelia in many other contexts remains to be determined.
However, notably, two studies examining the localization of activated Notch1 during mouse neocortical development found that it was not uniform across the apical-basal extent of the neocortical VZ, but instead showed higher activation basally than apically (Ochiai et al., 2009 and Tokunaga et al., 2004). Another recent advance with respect to Notch signaling in vertebrate neural development relates to our increasing grasp of progenitor heterogeneity in terms of gene expression and signaling. Although the existence of numerous proliferative neural cell types, even within a given region, has long been appreciated, our understanding
as to how that heterogeneity is created has lagged behind. Fortunately, progress is being made through studies of both in the embryonic and postnatal brains (Corbin et al., 2008 and Suh et al., 2009). In the embryonic neocortex, there are at least two primary proliferative neural cell types, radial glial NSCs, which are located in the ventricular zone (VZ), Histone demethylase and INPs, a fraction of which are present in the VZ, while the majority are in the subventricular zone (SVZ) (Farkas and Huttner, 2008 and Pontious et al., 2008). The segregation of these two populations has been studied using time-lapse imaging of slice cultures (Noctor et al., 2001 and Noctor et al., 2004), and by gene expression analysis (Englund et al., 2005). Interestingly, many INPs express the transcription factor Tbr2 (Englund et al., 2005), which has recently been shown to be a target of Neurog2 (Ochiai et al., 2009), a finding that connects the Notch cascade to marker expression in a specific proliferative neural cell type. Although numerous molecular markers have been identified that distinguish neural stem/progenitor cell subtypes in the embryo, and in the adult, less is known about signaling heterogeneity. With respect to Notch, our own work using a transgenic Notch reporter (TNR) mouse line has found that signal transduction is differentially regulated in specific subsets of cells in the telencephalic germinal zone (Mizutani et al.