Article

Signaling in adult neurogenesis: From stem cell niche to neuronal networks

Technische Universität München, München, Bavaria, Germany
Current Opinion in Neurobiology (Impact Factor: 6.77). 07/2007; 17(3):338-44. DOI: 10.1016/j.conb.2007.04.006
Source: PubMed

ABSTRACT The mechanisms that determine why neurogenesis is restricted to few regions of the adult brain in mammals, in contrast to its more widespread nature in other vertebrates such as zebrafish, remain to be fully understood. The local environment must provide key signals that instruct stem cell and neurogenic fate, because non-neurogenic progenitors can be instructed towards neurogenesis in this environment. Here, we discuss the recent progress in understanding key factors in the local stem cell niche of the adult mammalian brain, including surprising sources of new signals such as endothelial cells, complement factors and microglia. Moreover, new insights have been gained into how neuronal diversity is instructed in adult neurogenesis, prompting a new view of stem and progenitor cell heterogeneity in the adult mammalian brain.

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    • "Adult neurogenesis was first characterized in rodents in the 1960s (Altman 1969; Altman and Das 1965), with further attention in the 1990s from a reproductive perspective in song birds (Alvarez-Buylla 1992; Goldman and Nottebohm 1983). Since then, the idea of new neuron formation in adulthood has been widely accepted and in rodents, the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) have been regarded as the most prominent neurogenic niches in adulthood (Christian et al. 2014; Lepousez et al. 2013; Ninkovic and Gotz 2007; Rakic 2002; Suh et al. 2009). The hippocampal neurogenesis is found to be important for a series of hippocampus-dependent cognitive functions (Clelland et al. 2009; Sahay et al. 2011), as well as emotional regulation responses of antidepressants (Sahay and Hen 2007), while the SVZ-generated neurons migrate to the olfactory bulb through the rostral migratory stream (RMS). "
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    ABSTRACT: Adult neurogenesis in rodents has been extensively studied. Here we briefly summarized the studies of adult neurogenesis based on non-human primates and human postmortem brain samples. The differences between rodent, primate and human neurogenesis were discussed.
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    • ", 2006 ; Grandel et al . , 2006 ; Ninkovic and Götz , 2007 ; Pelegrini et al . , 2007 ; Kaslin et al . "
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    ABSTRACT: Adult neurogenesis is a widespread trait of vertebrates; however, the degree of this ability and the underlying activity of the adult neural stem cells differ vastly among species. In contrast to mammals that have limited neurogenesis in their adult brains,zebrafish can constitutively produce new neurons along the whole rostrocaudal brain axis throughout its life.This feature of adult zebrafish brain relies on the presence of stem/progenitor cells that continuously proliferate,and the permissive environment of zebrafish brain for neurogenesis. Zebrafish has also an extensive regenerative capacity, which manifests itself in responding to central nervous system injuries by producing new neurons to replenish the lost ones. This ability makes zebrafish a useful model organism for understanding the stem cell activity in the brain, and the molecular programs required for central nervous system regeneration.In this review, we will discuss the current knowledge on the stem cell niches, the characteristics of the stem/progenitor cells, how they are regulated and their involvement in the regeneration response of the adult zebrafish brain. We will also emphasize the open questions that may help guide the future research.
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    • "Astrocytes present a potential source of Notch as well as its ligands (Hitoshi et al., 2002; John et al., 2002; Wang et al., 2009), which are both membrane-bound molecules. Notch signaling is a direct result of cell-cell interactions in the neurogenic niche (Ninkovic and Gotz, 2007). Notch expression is enriched in both the SGZ and the SVZ (Breunig et al., 2007). "
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    ABSTRACT: Adult neurogenesis is an exceptional feature of the adult brain and in an intriguing way bridges between neuronal and glial neurobiology. Essentially, all classes of glial cells are directly or indirectly linked to this process. Cells with astrocytic features, for example, serve as radial glia-like stem cells in the two neurogenic regions of the adult brain, the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, producing new neurons, create a microenvironment permissive for neurogenesis, and are themselves generated alongside the new neurons in an associated but independently regulated process. Oligodendrocytes are generated from precursor cells intermingled with those generating neurons in an independent lineage. NG2 cells have certain precursor cell properties and are found throughout the brain parenchyma. They respond to extrinsic stimuli and injury but do not generate neurons even though they can express some preneuronal markers. Microglia have positive and negative regulatory effects as constituents of the "neurogenic niche". Ependymal cells play incompletely understood roles in adult neurogenesis, but under certain conditions might exert (back-up) precursor cell functions. Glial contributions to adult neurogenesis can be direct or indirect and are mediated by mechanisms ranging from gap-junctional to paracrine and endocrine. As the two neurogenic regions differ between each other and both from the non-neurogenic rest of the brain, the question arises in how far regionalization of both the glia-like precursor cells as well as of the glial cells determines site-specific "neurogenic permissiveness." In any case, however, "neurogenesis" appears to be an essentially glial achievement.
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