As both PDGF and EGF pathways are frequently affected in human brain tumors, dissecting the differing effects of these two stimuli on the properties of immature cells may offer insight into the invasive and proliferative properties of distinct classes of gliomas. In fact, recent work suggests that deregulation of proliferation or oncogenic mutations within progenitor populations of the VZ-SVZ

could lead to brain tumor formation (Persson et al., 2002, Zhu et al., 2005, Zheng et al., 2008, Alcantara Llaguno et al., 2009 and Jacques et al., 2010). Another subset of the receptor tyrosine kinase family, ephrin receptors, is also http://www.selleck.co.jp/products/CHIR-99021.html active in the adult VZ-SVZ. Eph receptors and

their transmembrane ephrin ligands function in guidance of migratory cells and establishment of boundaries in developing tissues. Within the adult VZ-SVZ, both EphB and EphA receptors are expressed, and ephrin signaling appears to impact both type B cell proliferation and type A cell migration (Conover et al., 2000, Liebl et al., 2003 and Ricard et al., 2006). Infusion of EphB2 ligand results in disrupted and aberrant chains of migratory neuroblasts and also in increased BrdU incorporation by type B1 cells. Intriguingly, infusion also appears to increase the number of stem cells contacting the ventricle, possibly indicating increased PI3K Inhibitor Library ic50 type B1 cell activation. More recently, EphB2 signaling has also been suggested to act downstream of Notch signaling to maintain ependymal cell identity and regulate the conversion of ependymal cells to astrocytes after injury to the ventricular face (Nomura et al., 2010). EphA4 signaling has been proposed to about act as an anti-apoptotic signal within the adult VZ-SVZ, as removal of ephrinB3 in the adult results

in increased apoptosis (Furne et al., 2009). EGFR signaling has also been proposed to modulate Notch signaling—a fundamental pathway in nervous system development (Aguirre et al., 2010). Notch is essential for maintaining asymmetric division and stem cell pools in multiple tissues (Maillard et al., 2003 and Mizutani et al., 2007). In the adult VZ-SVZ, loss of Notch signaling compromises stem cell self-renewal, while activation of this pathway enhances neurosphere formation (Hitoshi et al., 2002 and Alexson et al., 2006). Postnatal deletion of Numb/Numblike, which inhibit Notch signaling by mediating degradation of the Notch protein, has also been shown to affect the VZ-SVZ niche. Acute deletion of Numb/Numbl in nestin-positive VZ-SVZ cells resulted in extensive defects in maturation of the neonatal VZ/SVZ, alterations in ependymal cell maturation and adhesion, and decreased neuroblast survival, likely due to excess Notch activity (Kuo et al., 2006).