Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal

Abstract

Neural stem cells (NSCs) in the postnatal mammalian brain self-renew and are a source of neurons and glia. To date, little is known about the molecular and cellular mechanisms regulating the maintenance and differentiation of these multipotent progenitors. We show that Jagged1 is required by mitotic cells in the subventricular zone (SVZ) and stimulates self-renewal of multipotent epidermal growth factor-dependent NSCs. Jagged1-expressing cells line the adult SVZ and are juxtaposed to Notch1-expressing cells, some of which are putative NSCs. In vitro, endogenous Jagged1 acts through Notch1 to promote NSC maintenance and multipotency. In vivo, reducing Jagged1/Notch1 signaling decreases the number of proliferating cells in the SVZ. In addition, soluble Jagged1 promotes self-renewal and neurogenic potential of multipotent neural progenitors in vitro. Our findings suggest a central role for Jagged1 in the NSC niche in the SVZ for maintaining a population of NSCs in the postnatal brain.

The niche of stellate cells within rat liver

“…The expression of Notch1 by HSCs and the synthesis of its ligand Jag1 by parenchymal cells further support the novel concept of a stellate cell niche in the liver, because stem cell neighbors synthesize Jag1 to support self-renewal of stem cells via Notch1 within the niche. 26 The relevance of this signaling pathway for HSCs is currently unknown; however, due to the typical distribution of Jag1 and Notch1, which is consistently found in stem cell niches, and the expression of Notch target genes (Hes1, Heyl) by HSC, Notch signaling was included in the scheme of the stellate cell niche (Fig. 6).…”

“…These signaling pathways maintain properties of stem/progenitor cells such as self-renewal by slow and symmetric cell divisions without differentiation. 25,26 Stem cells within their niche are normally quiescent and stay in G 0 of the cell cycle. In the normal liver, stellate cells are also in G 0 as indicated by the absence of Ki-67 synthesis of freshly isolated HSCs of rats.…”

Neurogenic Subventricular Zone Stem/Progenitor Cells Are Notch1-Dependent in Their Active But Not Quiescent State

“…1E,F), and early Dcx ϩ neuroblasts (Fig. 1G) (Nyfeler et al, 2005;Givogri et al, 2006;Carlén et al, 2009). Therefore, Notch1 is expressed by SVZ progenitors at different stages of differentiation from NSCs to neuroblasts and astrocytes.…”

Notch 2 and Notch 1/3 segregate to neuronal and glial lineages of the developing olfactory epithelium

“…Its role in progenitor maintenance is supported by Notch 1 mRNA expression in the embryonic ventricular zone, along with its effector Hes-5 and multiple ligands Jagged 1 and Delta-like 1 and 3. Postnatally, Notch 1 has been detected in scattered cells within the subventricular zone (SVZ) progenitor-containing niche, in the vicinity of Jagged-1 expressing cells (Irvin et al, 2001(Irvin et al, , 2004Stump et al, 2002;Nyfeler et al, 2005). In addition, Notch 1 and 3 contribute to gliogenesis (Tanigaki et al, 2001;Lutolf et al, 2002;Tokunaga et al, 2004).…”