Composition and Organization of the SCZ: A Large Germinal Layer Containing Neural Stem Cells in the Adult Mammalian Brain

Abstract

Two known germinal zones continue to generate new neurons and glia in the adult mammalian brain: the subventricular zone (SVZ), lining the lateral walls of the lateral ventricle, and the subgranular zone of the dentate gyrus. Here we describe a region we will refer to as the subcallosal zone (SCZ). The SCZ is a caudal extension of the SVZ that is no longer associated to an open ventricle. It lies between the hippocampus and the corpus callosum. Cells isolated from the SCZ and cultured as neurospheres behave as neural stem cells in vitro. Using electron and light microscopy, we describe the cell types present in this region and how their organization differs from that of the SVZ. Using retroviral labeling and homotypic-homochronic microtransplantation techniques, we show that the majority of cells born in the SCZ migrate into the corpus callosum to become oligodendrocytes in vivo. This study defines the organization and fate of cells born in a large germinal region of the adult forebrain.

In VivoAnalysis of Ascl1 Defined Progenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis

“…6C,D). Restriction of the GFP cells in a specific region within the corpus callosum suggests it identifies an adult oligodendrogenic region (Seri et al, 2006). Furthermore, the GFP cells are partially overlapping with the OPC markers PDGFR␣, Olig2 or Sox10, but not with the mature oligodendrocyte marker APC, indicating that Ascl1 is present in progenitors before the known early oligodendrocyte markers are detected (Fig.…”

“…The Ascl1 population forms a discrete layer of cells along the ventral side of the corpus callosum, a region reported to be enriched in progenitor cells in the adult brain (Seri et al, 2006). Other oligodendrocyte markers including those considered early markers such as PDGFR␣ and Olig2 do not show this distinct pattern, but rather are distributed throughout the corpus callosum.…”

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…While the SGZ in the dentate gyrus has been characterized as a niche in vitro (Seaberg and van der Kooy, 2002;Becq et al, 2005;Bull and Bartlett, 2005) and in vivo (Nakatomi et al, 2002), these studies suggest that the CA1 region contains multipotent stem cells while the SGZ contains only precursors. Second, there is evidence for neural stem cell populations in the embryonic and adult cerebellum (Laywell et al, 2000;Klein et al, 2005) and between the hippocampus and corpus callosum in the subcollosal zone (SCZ) (Seri et al, 2006), although the composition of these potential niches is unknown. Finally, it has been suggested that there is an additional adult neural stem cell population distributed widely throughout the CNS.…”

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

“…Two known germinal zones continue to generate new neurons and glia in the adult mammalian brain: the subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus of the hippocampus Gage, 2000;Ming and Song, 2005;Santarelli et al, 2003). Besides the SVZ and SGZ, a large number of proliferating cells are found between the hippocampus and the corpus callosum in the adult rodent brain, a region that has recently been named as the subcallosal zone (Seri et al, 2006). These regions contain stem cells that can be isolated and grown in vitro as neurospheres, maintaining self-renewal and multipotentiality over time (Gage et al, 1998;Gritti et al, 2002;Reynolds and Weiss, 1992).…”

“…To study the mechanisms by which the serotonergic system may impact on their functional features, we applied a standardized in vitro assay (NeuroSphere Assay, NSA) (Gritti et al, 1996(Gritti et al, , 1999Reynolds and Rietze, 2005;Reynolds and Weiss, 1992;Seri et al, 2006) to isolate and expand ANSC grown in neurospheres from the mouse hippocampus. We showed that inhibition of 5-HT synthesis by TPH inactivation caused a dramatic fall in ANSC proliferation, which could be rescued by adding exogenous 5-HT.…”