Adult neurogenesis: mechanisms and functional significance

Braun, Simon M. G.; Jessberger, Sebastian

doi:10.1242/dev.104596

Cited by 154 publications

(128 citation statements)

References 57 publications

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“…The NSPC population in the SGZ neurogenic niche can be divided into two broad categories: (i) slowly dividing stem cells, also known as radial glia-like cells (RGLs), and (ii) their more rapidly dividing progeny, transit-amplifying progenitors (TAPs) (2,18,19 Fig. S1D).…”

Section: Resultsmentioning

confidence: 99%

“…Hippocampal NSPCs are a heterogeneous population (2,18,19,49,50). How each of these subtypes of NSPCs is regulated has not been fully characterized, although some important players have been identified.…”

Section: Vehiclementioning

confidence: 99%

“…Resident neural stem and progenitor cells (NSPCs) in each of these areas proliferate and give rise to new neurons that migrate and integrate into existing circuitry in the olfactory bulb or dentate gyrus (DG), respectively. Particularly in the DG, where neurogenesis is found in both rodents and humans, newly born neurons play critical roles in facilitating memory function (1,2). This role of new neurons in memory is currently considered the dominant functional output of adult neurogenesis.…”

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confidence: 99%

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Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF

Kirby

Kuwahara

Messer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

129

100

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The adult hippocampus hosts a population of neural stem and progenitor cells (NSPCs) that proliferates throughout the mammalian life span. To date, the new neurons derived from NSPCs have been the primary measure of their functional relevance. However, recent studies show that undifferentiated cells may shape their environment through secreted growth factors. Whether endogenous adult NSPCs secrete functionally relevant growth factors remains unclear. We show that adult hippocampal NSPCs secrete surprisingly large quantities of the essential growth factor VEGF in vitro and in vivo. This self-derived VEGF is functionally relevant for maintaining the neurogenic niche as inducible, NSPC-specific loss of VEGF results in impaired stem cell maintenance despite the presence of VEGF produced from other niche cell types. These findings reveal adult hippocampal NSPCs as an unanticipated source of an essential growth factor and imply an exciting functional role for adult brain NSPCs as secretory cells.adult neurogenesis | vascular endothelial growth factor | stem cell | hippocampus | neural precursor

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Section: Resultsmentioning

confidence: 99%

Section: Vehiclementioning

confidence: 99%

mentioning

confidence: 99%

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Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF

Kirby

Kuwahara

Messer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

129

100

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“…Neural stem cells of these niches can be activated to divide and generate other stem cells, astrocytes, or new neurons (4,5). Newborn neurons of the dentate gyrus have the capacity to integrate into the existing hippocampal circuitry (6)(7)(8), influencing processes such as learning and memory (9)(10)(11) as well as stress and depression (12).…”

mentioning

confidence: 99%

Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

Moss

Gebara

Bushong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

108

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Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP-positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.adult neurogenesis | adult neural stem cell | neurogenic niche | electron microscopy | hippocampus N eurogenesis in the adult mouse brain primarily occurs within discrete niches, the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus, supplying new neurons to the olfactory bulb and the dentate gyrus, respectively (1-3). Neural stem cells of these niches can be activated to divide and generate other stem cells, astrocytes, or new neurons (4, 5). Newborn neurons of the dentate gyrus have the capacity to integrate into the existing hippocampal circuitry (6-8), influencing processes such as learning and memory (9-11) as well as stress and depression (12).Radial glia-like (RGL) neural stem cells of the SVZ, which supply the olfactory bulb with newborn neurons and astrocytes, express astrocytic markers and form elegant pinwheel structures (13-16). RGL neural stem cells of the adult dentate gyrus also express astrocytic markers, but comprise a heterogeneous population based on the molecular markers they express, the morphologies they exhibit (17-22), and their fate (23-28). Nestin-GFP-positive RGL stem cells account for more than 70% of RGL stem cells in the SGZ of the dentate gyrus (24), but it was recently found that not all Nestin-GFP-positive cells with RGL morphology have stem cell properties (29): type β cells, which arborize in the granule cell layer (GCL) but do not reach the molecular layer (ML) of the dentate gyrus, account for 26% of Nestin-GFP-positive RGL stem cells. They express stem cell (Sox1, Sox2, Prominin 1, GFAP, and Nestin) and astrocytic [GFAP, glial glutamate tranporter 1 (GLT1), and S100β] markers but do not proliferate. In contrast, type α cells, which extend across the GCL and arborize in the inner ML, account for 74% of Nestin-GFP-positive RGL cells. They express stem...

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“…The adult mammalian brain contains stem cells that continuously produce new neurons (Braun and Jessberger, 2014). When these stem cells were first discovered, many hoped that they would be similar to those previously found in other organs and that they would be able to repair injuries and replace lost or damaged neurons in many parts of the brain.…”

Section: Introductionmentioning

confidence: 99%

Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions

Magnusson

Frisén

2016

Development

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In a few regions of the adult brain, specialized astrocytes act as neural stem cells capable of sustaining life-long neurogenesis. In other, typically non-neurogenic regions, some astrocytes have an intrinsic capacity to produce neurons when provoked by particular conditions but do not use this ability to replace neurons completely after injury or disease. Why do astrocytes display regional differences and why do they not use their neurogenic capacity for brain repair to a greater extent? In this Review, we discuss the neurogenic potential of astrocytes in different brain regions and ask what stimulates this potential in some regions but not in others. We discuss the transcriptional networks and environmental cues that govern cell identity, and consider how the activation of neurogenic properties in astrocytes can be understood as the de-repression of a latent neurogenic transcriptional program.

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Adult neurogenesis: mechanisms and functional significance

Cited by 154 publications

References 57 publications

Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF

Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF

Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions

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