Notch in the Vertebrate Nervous System: An Old Dog with New Tricks Tarran Pierfelice, Lavinia Alberi, Nicholas Gaiano  Neuron  Volume 69, Issue 5, Pages 840-855 (March 2011) DOI: 10.1016/j.neuron.2011.02.031 Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 1 Schematic of the Core Elements of the Notch Signaling Pathway Notch signaling occurs between two adjacent cells as depicted. Only a subset of the pathway elements are shown for clarity and to highlight the fundamental components. A more complete schematic can be found in another recent review (Kopan and Ilagan, 2009). The site of S2 ligand-dependent processing is shown (arrowhead), as is the site of the γ-secretase-PS1/2-mediated S3 cleavage (gray arrow). Ub, ubiquitin; PS, Presenilin. Neuron 2011 69, 840-855DOI: (10.1016/j.neuron.2011.02.031) Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 2 Notch Signaling during Neocortical Development: A Revised View The neocortical germinal zone (VZ and SVZ) contain multiple proliferative cell types. Notch signaling is differentially utilized among these cells as suggested by EGFP expression in the TNR mouse line (Mizutani et al., 2007). In addition, Notch activation in VZ cells is driven by ligand expression and Mib1 function in SVZ cells (Yoon et al., 2008). NSC, neural stem cell; INP, intermediate neural progenitor; BP, basal progenitor; Mib1, Mindbomb1; Dll1, Delta-like 1; VZ, ventricular zone; SVZ, subventricular zone. Neuron 2011 69, 840-855DOI: (10.1016/j.neuron.2011.02.031) Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 3 The Dynamics of Hes1 in Neocortical Progenitors (A) Oscillations in Hes1 expression are driven by a negative autoregulatory feedback loop (Shimojo et al., 2008). The periodicity of these cycles is about 2 hr, and they lead to the cyclical expression of Neurogenin2 (Neurog2) and Delta-like 1 (Dll1). (B) Early in neocortical development, many adjacent cells are equivalent, and have cycling Hes1, Neurog2, and Dll1. (C) Interactions between adjacent cells will fix the gene expression status of those cells, such that some will become intermediate progenitors and neurons, while other will remain as NSCs. Neuron 2011 69, 840-855DOI: (10.1016/j.neuron.2011.02.031) Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 4 Notch in Adult SVZ Neurogenesis Notch signaling can block the proliferation of ependymal cells (Carlén et al., 2009), but leads to expansion of the NSC pool (type B cells) in the SVZ (also sometimes called the subependymal layer) (Aguirre et al., 2010). EGFR signaling can increase the number of transit amplifying progenitors (TAPs, or type C cells), and that increase in turn leads to reduced self-renewal of NSCs. Also depicted is the recent finding that the pigmented epithelium derived factor (PEDF) can enhance Notch signaling in SVZ NSCs (Andreu-Agulló et al., 2009). Neuron 2011 69, 840-855DOI: (10.1016/j.neuron.2011.02.031) Copyright © 2011 Elsevier Inc. Terms and Conditions