, 2006). These results point to the importance of identifying SVZ niche-specific pathways to allow for direct deletion

of SVZ architecture without cell intrinsically affecting NSCs. Little is known about the molecular mechanisms controlling SVZ generation from embryonic progenitors. Shortly before and after birth, while most embryonic radial glia terminally differentiate, postnatal radial glial progenitors (pRGPs) along the lateral walls of lateral ventricles generate the SVZ niche (Tramontin et al., 2003). The transformation from embryonic to adult neurogenesis is mediated by a subpopulation RG7204 ic50 of pRGPs differentiating into SVZ NSCs (Merkle et al., 2004). A second subpopulation of pRGPs gives rise to ependymal cells that form the new epithelial lining of the brain ventricles, which also serve as multiciliated

niche cells for the SVZ NSCs (Spassky et al., 2005). We showed previously that during terminal differentiation Volasertib chemical structure of pRGPs, progenitors begin to modify their lateral membrane contacts (Kuo et al., 2006). The Ankyrin family of proteins in mammals, consisting of Ankyrin R (1, Ank1), B (2, Ank2), and G (3, Ank3), are large adaptor molecules that organize membrane domains in a number of different cell types, including erythrocytes, cardiac and skeletal muscles, epithelial cells, retinal photoreceptors, and neuronal axon initial segments (Bennett and Healy, 2008). Although Ankyrins and their homologs in other model organisms have not been linked to stem cell niche functions, Ank3 is known to regulate lateral membrane biogenesis of bronchial epithelial cells, through collaborative interactions with β2-Spectrin and α-Adducin (Kizhatil and Bennett, 2004 and Abdi (-)-p-Bromotetramisole Oxalate and

Bennett, 2008). Using in vivo-inducible genetics and newly developed in vitro assays, we revealed a function for Ank3 and its upstream regulator in radial glial assembly of adult SVZ niche, which upon disruption led to the complete absence of SVZ ependymal niche in vivo. The revelation of these key early molecular steps allowed us to address fundamental questions about SVZ organization on continued production of new neurons. Since the SVZ niche is formed during postnatal maturation of the brain ventricular wall, we performed surface-scanning electron microscopy and transmission electron microscopy (TEM) on mouse brains from postnatal days 0, 7, and 14 to observe anatomical changes (P0, P7, and P14, respectively; see Figure S1A available online). Unlike the medial wall surface, which showed abundant multiciliated cells throughout, at P0 the cells on the lateral wall were predominantly monociliated and gradually became multiciliated over the next 2 weeks.