Neural Stem Cells Confer Unique Pinwheel Architecture to the Ventricular Surface in Neurogenic Regions of the Adult Brain

Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell stem cell (Impact Factor: 22.27). 10/2008; 3(3):265-78. DOI: 10.1016/j.stem.2008.07.004
Source: PubMed


Neural stem cells (NSCs, B1 cells) are retained in the walls of the adult lateral ventricles but, unlike embryonic NSCs, are displaced from the ventricular zone (VZ) into the subventricular zone (SVZ) by ependymal cells. Apical and basal compartments, which in embryonic NSCs play essential roles in self-renewal and differentiation, are not evident in adult NSCs. Here we show that SVZ B1 cells in adult mice extend a minute apical ending to directly contact the ventricle and a long basal process ending on blood vessels. A closer look at the ventricular surface reveals a striking pinwheel organization specific to regions of adult neurogenesis. The pinwheel's core contains the apical endings of B1 cells and in its periphery two types of ependymal cells: multiciliated (E1) and a type (E2) characterized by only two cilia and extraordinarily complex basal bodies. These results reveal that adult NSCs retain fundamental epithelial properties, including apical and basal compartmentalization, significantly reshaping our understanding of this adult neurogenic niche.

  • Source
    • "The CP also secretes Slit2, the critical molecule in guiding NSPCs' migration in the SVZ, into the CSF (Hu 1999;Wu et al., 1999). The type-B cells in the SVZ extend their primary cilium into the ventricle space and thus are in direct contact with the CSF (Gil-Perotin et al., 2009;Han et al.,Ming and Song, 2005;Mirzadeh et al., 2008). Considering the unique anatomical connection between the CP and SVZ through the CSF, we propose that there is a " CP-CSF-SVZ " epithelia-ventricle-interactive lineage axis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adult neurogenesis occurs in brain subventricular zone (SVZ). Our recent data reveal an elevated proliferation of BrdU(+) cells in SVZ following subchronic manganese (Mn) exposure in rats. This study was designed to distinguish Mn effect on the critical stage of adult neurogenesis, i.e., proliferation, migration, survival and differentiation from the SVZ via the rostral migratory stream (RMS) to the olfactory bulb (OB). Adult rats received a single ip-dose of BrdU at the end of 4-wk Mn exposure to label proliferating cells. Immunostaining and cell-counting showed a 48% increase of BrdU(+) cells in Mn-exposed SVZ than in controls (p<0.05). These BrdU(+) cells were identified as a mixed population of mainly GFAP(+) type-B neural stem cells with Nestin(+) type-C transit progenitor cells, DCX(+) migratory neuroblasts and Iba1(+) microglial cells. Another group of adult rats received 3 daily ip-injections of BrdU followed by subchronic Mn exposure. By 4-wk post BrdU labeling, most of the surviving BrdU(+) cells in the OB were differentiated into NeuN(+) matured neurons. However, survival rates of BrdU/NeuN/DAPI triple-labeled cells in OB were 33% and 64% in Mn-exposed and control animals, respectively (p<0.01). Infusion of Cu directly into the lateral ventricle significantly decreased the cell proliferation in the SVZ. Taken together, these results suggest that Mn exposure initially enhances the cell proliferation in adult SVZ mainly by increasing type-B cells. In the OB, however, Mn exposure significantly reduces the surviving adult-born cells and markedly inhibits their differentiation into mature neurons, resulting in an overall decreased adult neurogenesis in the OB.
    Full-text · Article · Jan 2016 · Toxicological Sciences
  • Source
    • "nd differentiation capacities . Radial glial NSCs—the so - called type B cells—extend an apical ending that is exposed to the ventricle and possess a long basal process ending on blood vessels ( Mirzadeh et al . , 2010 ) . These cells are surrounded by multiple ependymal cells ( type E cells ) forming pinwheel structures on the ventricle surface ( Mirzadeh et al . , 2008 ) . Type B cells divide slowly to generate transit - amplifying type C cells , which proliferate actively and further differentiate into neuroblasts also named type A cells . Finally , these cells form chains and migrate over long distances toward the olfactory bulb ( OB ) , via the rostral migratory stream ( RMS ) . In the OB , neurobl"
    [Show abstract] [Hide abstract]
    ABSTRACT: Stroke affects one in every six people worldwide, and is the leading cause of adult disability. After stroke, some limited spontaneous recovery occurs, the mechanisms of which remain largely unknown. Multiple, parallel approaches are being investigated to develop neuroprotective, reparative and regenerative strategies for the treatment of stroke. For years, clinical studies have tried to use exogenous cell therapy as a means of brain repair, with varying success. Since the rediscovery of adult neurogenesis and the identification of adult neural stem cells in the late nineties, one promising field of investigation is focused upon triggering and stimulating this self-repair system to replace the neurons lost following brain injury. For instance, it is has been demonstrated that the adult brain has the capacity to produce large numbers of new neurons in response to stroke. The purpose of this review is to provide an updated overview of stroke-induced adult neurogenesis, from a cellular and molecular perspective, to its impact on brain repair and functional recovery.
    Full-text · Article · Dec 2015 · Frontiers in Neuroscience
  • Source
    • "Recent studies indicate the importance of astrocyte-like cells and tanycyte-like ependymal cells lining the brain ventricle for neurogenesis and gliogenesis. Astrocyte-like B1 NSCs in the subependymal zone of the SVZ are surrounded by ependymal cells to form a unique rosette or pinwheel-like structure (Mirzadeh et al. 2008). Spatial association of NSCs and ependymal cells provides a special micro-environment niche for mitosis of NSCs that is characterized by expression of collagen IV, β1 and γ1 laminin, fibroblast growth factor (FGF)-2, and matrix metalloprotease (Kerever et al. et al. 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adja- cent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions.
    Full-text · Article · Nov 2015 · Cell and Tissue Research
Show more