Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling.
ABSTRACT 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.
Article: Distinctive population of[Show abstract] [Hide abstract]
ABSTRACT: In the adult hippocampus, granule cells continue to be generated from astrocyte‐like progenitors expressing glial fibrillary acidic protein (GFAP) that differ from embryonic neocortical progenitors. However, during the embryonic period, dentate granule neurons and neocortical pyramidal neurons are derived from the ventricular zone (VZ) of the pallium. Our question is when do GFAP+ progenitors of granule neurons appear in the developing hippocampus during the embryonic period, and how do they form the granule cell layer. The present analysis using Gfap‐GFP transgenic mice shows that the GFP+ distinct cell population first appears in the VZ of the medial pallium at the dorsal edge of the fimbria on embryonic day 13.5. During the perinatal period, they form a migratory stream from the VZ to the developing dentate gyrus, and establish the germinal zones in the migratory stream, and the marginal and hilar regions in the developing dentate gyrus. GFP+ cells in these regions were positive for Sox2 and Ki67, but negative for BLBP. GFP+ cells with Neurogenin2 expression were largely distributed in the VZ, whereas GFP+ cells with Tbr2 and NeuroD expressions were seen in the migratory stream and developing dentate gyrus. Prox1‐expressing GFP+ cells were restricted to the developing dentate gyrus. These results suggest that distinctive Gfap‐expressing progenitors arising around the dentate notch form germinal regions in the migratory stream and the developing dentate gyrus where they differentiate into granule neurons, indicating that distinct astrocyte‐like neural progenitors continue to generate granule neurons, from the beginning of dentate development and throughout life. J. Comp. Neurol. 522:261–283, 2014. © 2013 Wiley Periodicals, Inc.The Journal of Comparative Neurology 01/2014; 522(2). · 3.51 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signaling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells (NSCs) are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signaling, for instance, regulates NSC behavior both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors (TFs) and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult NSCs in this region.Frontiers in Cellular Neuroscience 01/2014; 8:396. · 4.18 Impact Factor
- [Show abstract] [Hide abstract]
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 04/2014; 522(15). · 3.51 Impact Factor