, 2008). Some signals commonly determine cell fate decisions in the nervous and vascular system. For instance, VEGF and Notch regulate neurogenic commitment of neural stem cells (NSCs)

(Pierfelice et al., 2011) as well as endothelial arterial/venous cell fate specification (Swift and Weinstein, 2009). Genetic studies in zebrafish show that VEGF upregulates Notch expression to drive arterial EC differentiation during development. In the PNS, VEGF produced by Schwann cells determines arterial specification of ECs in cotracking vessels (Ruiz de Almodovar et al., 2009). Notch determines arterial development, as illustrated by the loss of arterial identity of SMCs resulting in a venous-like appearance of cerebral arteries (thinner ABT-263 purchase media, dilated lumen) upon SMC-selective disruption of Notch (Gridley, 2010). In these mice, the anterior communicating arteries in the circle of Willis fail to anastomose, impairing collateral blood flow and rendering them vulnerable to cerebral artery occlusion. While neural cells stimulate vessel growth by releasing VEGF and other angiogenic factors, vessels also crosstalk to neural cells, not only by functioning as conduits for oxygen and nutrient supply, GSK3 inhibitor but also by releasing angiocrine

signals to promote neuronal development (Butler et al., 2010). This seems to be particularly the case in the neurogenic niche, where periventricular vessels develop coincidently with the onset of cortical neurogenesis (Vasudevan et al., 2008). much Consistent with reports that hypoxia promotes stemness (Mohyeldin et al., 2010), NSCs reside in a hypoxic neurogenic niche in the ventricular zone at a

distance from the vascular supply (Mazumdar et al., 2010) (Figure 4A). Basal progenitors, already committed to the neuronal lineage, leave the avascular part and migrate toward the vascular plexus in the adjacent subventricular zone (Johansson et al., 2010). Intriguingly, vessels invade the subventricular germinal zone when the first basal progenitors arise (Vasudevan et al., 2008). These progenitors become aligned with vessels and undergo neurogenic divisions in close vicinity of vessel branch points. In contrast, divisions that generate NSCs or basal progenitors to expand the pool of stem and progenitor cells take place in the less vascularized part of the ventricular zone (Johansson et al., 2010). These spatial and temporal patterns suggest a role for vessels in the neurogenic niche to coordinate neurogenesis, but how oxygen and/or vessel-derived signals fine-tune this process and which angiocrine molecular signals are involved requires further study. In line, cultured ECs release signals that stimulate proliferation of neural precursors and bias their differentiation to a neuronal fate (Shen et al., 2004).