The specific “mix” of intrinsic factors that characterizes distinct neural stem cell function and identity acts in conjunction with a local “mix” of extracellular signaling molecules bathing NSCs. There are four major classes of secreted extracellular signaling molecules that are expressed in the developing brain during embryogenesis and that participate in the patterning of the nervous system – FGFs, WNTs, Sonic Hedgehog (SHH) and Bone Morphogenetic Proteins (BMP). FGFs diffuse from the anterior neural ridge, a region corresponding later in development to the commissural plate, which is the foremost rostral boundary of the telencephalon; WNTs and BMPs emanate from the cortical hem, comprising the medial margin of each hemisphere; BMPs are secreted from the roof plate, the dorsal region in between the cerebral hemispheres; and SHH diffuses from the ventral portion of the neural tube or floor plate (Figure 2). In addition to these long-range signals, the balance between Notch ligands and Notch receptors, which are membrane bound, strongly influences neural stem cell fate (Johnson et al., 2009a). Extracellular signals shape CNS morphogenesis and regulate cell fate by influencing the specific “mix” of intrinsic factors present at specific locations and times in the developing CNS (Figure 1).