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.

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    • "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). "
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    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.
    Cell and Tissue Research 11/2015; 362:337-365. DOI:10.1007/s00441-015-2201-0 · 3.57 Impact Factor
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    • "Multiciliated ECs have a prominent role in the maintenance of the neurogenic niche, since they induce neurogenesis and suppress gliogenesis by secreting the bone morphogenetic protein (BMP) inhibitor, Noggin (Lim et al., 2000; Chmielnicki et al., 2004). ECs are defined as large-apical surface multiciliated cells that express S100ß and Vimentin (Spassky et al., 2005; Raponi et al., 2007; Mirzadeh et al., 2008; Pastrana et al., 2009). ECs are generated from RG in a multistep process orchestrated by the primary cilium and its basal body apparatus (Spassky et al., 2005). "
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    ABSTRACT: The adult subventricular zone (SVZ) is a highly organized microenvironment established during the first postnatal days when radial glia cells begin to transform into type B-cells and ependymal cells, all of which will form regenerative units, pinwheels, along the lateral wall of the lateral ventricle. Here, we identify p73, a p53 homologue, as a critical factor controlling both cell-type specification and structural organization of the developing mouse SVZ. We describe that p73 deficiency halts the transition of the radial glia into ependymal cells, leading to the emergence of immature cells with abnormal identities in the ventricle and resulting in loss of the ventricular integrity. p73-deficient ependymal cells have noticeably impaired ciliogenesis and they fail to organize into pinwheels, disrupting SVZ niche structure and function. Therefore, p73 is essential for appropriate ependymal cell maturation and the establishment of the neurogenic niche architecture. Accordingly, lack of p73 results in impaired neurogenesis. Moreover, p73 is required for translational planar cell polarity establishment, since p73 deficiency results in profound defects in cilia organization in individual cells and in intercellular patch orientation. Thus, our data reveal a completely new function of p73, independent of p53, in the neurogenic architecture of the SVZ of rodent brain and in the establishment of ependymal planar cell polarity with important implications in neurogenesis. This article is protected by copyright. All rights reserved.
    Developmental Neurobiology 10/2015; DOI:10.1002/dneu.22356 · 3.37 Impact Factor
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    • "Neural stem cells (NSCs) are residing in niches along the ventricular neuraxis of the mammalian nervous system (Craig et al. 1996; Golmohammadi et al. 2008; Mirzadeh et al. 2008; Shen et al. 2008). They are capable of selfrenewal , prolonged cell division, and generating a large number of progeny (Reynolds and Weiss 1992). "
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    ABSTRACT: IntroductionNeural stem cells (NSCs) reside along the ventricular axis of the mammalian brain. They divide infrequently to maintain themselves and the down-stream progenitors. Due to the quiescent property of NSCs, attempts to deplete these cells using antimitotic agents such as cytosine b-Aarabinofuranoside (Ara-C) have not been successful. We hypothesized that implementing infusion gaps in Ara-C kill paradigms would recruit the quiescent NSCs and subsequently eliminate them from their niches in the subventricular zone (SVZ).Methods We infused the right lateral ventricle of adult mice brain with 2% Ara-C using four different paradigms—1: one week; 2: two weeks; 3, 4: two weeks with an infusion gap of 6 and 12 h on day 7. Neurosphere assay (NSA), neural colony-forming cell assay (N-CFCA) and immunofluorescent staining were used to assess depletion of NSCs from the SVZ.ResultsNeurosphere formation dramatically decreased in all paradigms immediately after Ara-C infusion. Reduction in neurosphere formation was more pronounced in the 3rd and 4th paradigms. Interestingly 1 week after Ara-C infusion, neurosphere formation recovered toward control values implying the presence of NSCs in the harvested SVZ tissue. Unexpectedly, N-CFCA in the 3rd paradigm, as one of the most effective paradigms, did not result in formation of NSC-derived colonies (colonies >2 mm) even from SVZs harvested 1 week after completion of Ara-C infusion. However, formation of big colonies with serial passaging capability, again confirmed the presence of NSCs.Conclusions Overall, these data suggest Ara-C kill paradigms with infusion gaps deplete NSCs in the SVZ more efficiently but the niches would repopulate even after the most vigorous kill paradigm used in this study.
    Brain and Behavior 10/2015; DOI:10.1002/brb3.404 · 2.24 Impact Factor
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