Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling

Department of Neurology, UCSF School of Medicine, San Francisco, CA 94158, USA.
Development (Impact Factor: 6.46). 02/2009; 136(2):327-35. DOI: 10.1242/dev.025742
Source: PubMed


One striking feature of dentate gyrus development, distinct from the other cortical structures, is the relocation of neural precursors from the ventricular zone to the forming dentate pole to produce a lifelong neurogenic subgranular zone (SGZ). In this study, we demonstrate that dentate progenitors first dwell for up to 1 week in a previously unrecognized neurogenic zone intimately associated with the pial meningeal surface lining the outer edge of the forming dentate. This zone also serves as the organizational matrix for the initial formation of the dentate glial scaffolding. Timely clearance of neural precursors from their transient location depends on reelin, whereas initial formation of this transient stem cell niche requires Cxcl12-Cxcr4 signaling. The final settlement of the neural precursors at the subgranular zone relies on a pertussis toxin-sensitive pathway independent of Cxcl12-Cxcr4 signaling. Furthermore, genetic fate-mapping analysis suggests that subpial precursors contribute to the SGZ formation. These results demonstrate that the relocation of neural precursors in the dentate gyrus consists of discrete steps regulated by multiple pathways.

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    • "First, the granule cells of the outer shell (Figure 1, blue) originate prenatally from the neuroepithelium (NE) located near the fimbria and migrate from the progressively receding secondary dentate matrix to the subpial zone (SPZ; Figure 1, blue). The first dentate migration (dgml) is the source of the earliest generated granule cells that will constitute the outer shell of the granular layer (Altman and Bayer, 1990a,b; Li et al., 2009). During the second postnatal phase (Figure 1, red), the precursor cells build up a new proliferation zone distributed within the hilus, and the early embryonic radial glial scaffold from the ventricular zone (VZ) is replaced by a secondary glial scaffold that traverses the hilus (Figure 1, green). "
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    Frontiers in Molecular Neuroscience 02/2015; 8:3. DOI:10.3389/fnmol.2015.00003 · 4.08 Impact Factor
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    • "We previously observed small number of cells expressing Prox1 weakly in E14.5 at around the dentate notch (Sugiyama et al., 2013). However, there are discrepancies in the onset of Prox1 expression, and some papers have reported earlier Prox1 expression in the medial telencephalon than our previous observation (Bagri et al., 2002; Galceran et al., 2000; Galichet et al., 2008; Hodge et al., 2012, 2013; Lavado et al., 2010; Li et al., 2009; Liu et al., 2000; Oliver et al., 1993; Seki et al., 2013; Sugiyama et al., 2013; Zhou et al., 2004). We improved our protocol to enhance sensitivity, and could detect Prox1 immunoreactivity at E11.5 (data not shown) and at E12.5 (Fig. 2C), but not at E10.5 (data not shown) in the medial telencephalon. "
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    ABSTRACT: The hippocampal formation (HF) is a unique structure in the mammalian brain and subdivided into the dentate gyrus, Ammon's horn, and subiculum by their functions and connectivity in the neuronal circuit. Because behaviors of the neural stem cells, neuronal progenitors, and the differentiating neurons are complex during hippocampal morphogenesis, the differentiation of these subdivisions has not been understood well. In this study, we investigated embryonic and postnatal expression of proteins Prox1, Math2, and Ctip2, which clearly indicate principal cells of the dentate gyrus (Prox1 positive) and Ammon's horn (Math2 and Ctip2 positive). Expression pattern of Prox1 and Math2 was consistent to previously suggested localization of migratory pathways of the dentate granule cells and hippocampal pyramidal cells. Interestingly, we found intermingling of Prox1 expressing cells and Math2 expressing cells in a cell migratory stream, suggesting previously unknown behaviors of differentiating cells of the HF. J. Comp. Neurol., 2014. © 2014 Wiley Periodicals, Inc.
    The Journal of Comparative Neurology 10/2014; 522(15). DOI:10.1002/cne.23621 · 3.23 Impact Factor
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    • "During this time, newborn neurons populate the same anatomical space as cells born during adulthood, but at a considerably (up to 300%) higher rate (He and Crews, 2007). Finally in adulthood, which begins at approximately postnatal day 56 (P56), neurogenesis continues in the SGZ, but at a lower and continuously declining rate throughout life (Zhao et al., 2008; Li et al., 2009). In adolescent and adult mice SGZ neural precursors differentiate into new neurons and functionally integrate into the granule cell layer (Toni et al., 2008). "
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