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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    • "This could be explained by a non-cell autonomous induction of NSC quiescence by IPCs through Notch signaling, as shown in the case of Prox1 mutant mice (see below), although a more direct role of Tbr2, which is expressed by a small subset of NSCs, is not ruled out (Hodge et al., 2008, 2012). Prox1 is a homeobox TF expressed by multiple types of neuronal progenitors and postmitotic cells, including newly born granule cells in the tertiary matrix of the developing DG (Oliver et al., 1993; Li et al., 2009). Prox1 is often used as a marker of the dentate granule neuron lineage, although it is also expressed at low levels in some hippocampal interneurons (Rubin and Kessaris, 2013). "
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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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