Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Dev Biol
Impact Factor: 5.814

Developmental dynamics of neurogenesis and gliogenesis in the postnatal mammalian brain in health and disease: Historical and future perspectives

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Abstract The mature mammalian brain has long been thought to be a structurally rigid, static organ since the era of Ramón y Cajal in the early 20th century. Evidence accumulated over the past three decades, however, has completely overturned this long‐held view. We now know that new neurons and glia are continuously added to the brain at postnatal stages, even in mature adults of various mammalian species, including humans. Moreover, these newly added cells contribute to structural plasticity and play important roles in higher order brain function, as well as repair after damage. A major source of these new neurons and glia is neural stem cells (NSCs) that persist in specialized niches in the brain throughout life. With this new view, our understanding of normal brain physiology and interventional approaches to various brain disorders has changed markedly in recent years. This article provides a brief overview on the historical changes in our understanding of the developmental dynamics of neurogenesis and gliogenesis in the postnatal and adult mammalian brain and discusses the roles of NSCs and other progenitor populations in such cellular dynamics in health and disease of the postnatal mammalian brain. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease
Continuous production of new neurons from embryonic to adult stages in the mammalian brain. (a, b) Production of different subtypes of neurons in distinct progenitor domains of the embryonic mouse telencephalon. Panel a shows a representative lateral view of the embryonic brain, and panel b shows its view at a coronal plane (indicated by a white square in a). The light blue line in b indicates the areas where progenitors of new neurons reside. The embryonic primordia of the pallium, lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE), and septum (Sp) produce region‐specific projection neurons (blue arrows). The MGE also serves as the source of pallial (cortical) and striatal interneurons. The generation of these projection neurons and interneurons ceases by the end of embryogenesis. By contrast, the production of olfactory bulb (OB) interneurons and hippocampal dentate gyrus (DG) granule cells (red arrows) begins at embryonic stages and continues beyond birth in the postnatal and adult brain in rodents. Importantly, progenitor domains that produce OB interneurons partially overlap with those for region‐specific projection neurons. (c–h) Neurogenic/stem cell niches in the postnatal and adult mouse brain. Panel e shows a dorsolateral view of the adult mouse brain (anterior to the left). Panel f shows the locations of two neurogenic/stem cell niches, the ventricular–subventricular zone (VZ–SVZ) and hippocampal DG (areas indicated by light blue shades), in a parasagittal view. Panels c and d schematically show the anatomical relationships of the VZ–SVZ with other brain structures in a coronal plane indicated by the left vertical lines in e and f. Panels g and h show the location of the hippocampal DG in a coronal plane indicated by the right vertical lines in e and f. Panels c and h are magnified photographic views of the boxed areas in d and g, respectively. In all panels, areas shaded with light blue are where neural stem cells (NSCs) reside and produce new OB interneurons and DG granule cells (red arrows in c and h, respectively). Abbreviations: AC, anterior commissure; CC, corpus callosum; Cx, cortex; DG, dentate gyrus; LV, lateral ventricle; LGE, lateral ganglionic eminence; Hipp, hippocampus; MGE, medial ganglionic eminence; OB, olfactory bulb; POA, preoptic area; RMS, rostral migratory stream; Sp, septum; St, striatum; Th, thalamus; VZ–SVZ, ventricular‐subventricular zone
[ Normal View | Magnified View ]
Injury‐induced neurogenesis and gliogenesis in the postnatal and adult mammalian brain. In the intact brain, neural stem cells (NSCs) in the ventricular–subventricular zone (VZ–SVZ) and dentate gyrus (DG) selectively produce olfactory bulb interneurons (OB INs) (a) or DG granule cells (b), respectively (blue arrows). In response to various insults, however, those in the VZ–SVZ are thought to produce new neurons and glia (astrocytes and/or oligodendrocytes) that migrate to damaged areas such as the corpus callosum (CC), cerebral cortex (Cx), striatum (St), and hippocampal CA1 region (highlighted in red and green shades), and replace cells lost to insult (red arrows). The exact identity and functional properties of these cells, however, remain poorly understood. Abbreviations are the same as in Figure
[ Normal View | Magnified View ]
Production of astrocytes in the mammalian brain. (a) Two proposed models for the generation of astrocytes from radial glial progenitors (RGCs) in the developing cerebral cortex. (b) Proposed stepwise differentiation of astrocytes from RGCs. The features and representative expressed/regulatory genes of RGCs, astrocyte precursors (APs), and astrocytes are schematically shown. Like neuroblasts (NBs) and oligodendrocyte progenitor cells (OPCs) in the neuronal and oligodendrocyte lineages, the occurrence of an intermediate proliferative precursor cell type AP is speculated in the astrocyte lineage, but their exact identity is currently unknown. For details, see text. Abbreviations: MZ, mantle zone. Others are same as in Figure
[ Normal View | Magnified View ]
Continuous production of oligodendrocytes (OLs) from embryonic to adult stages in the mammalian brain. (a) The left panel schematically shows that multiple progenitor domains (preoptic area [POA], medial ganglionic eminence [MGE], lateral ganglionic eminence [LGE], and pallium) generate oligodendrocyte progenitor cells (OPCs) (red circles) at distinct embryonic stages in the developing mouse telencephalon. Red arrows indicate their migratory routes. The right panel schematically shows the sustained production of new OPCs (blue circles) in the ventricular–subventricular zone (VZ–SVZ) in the postnatal and adult brain, which exist as a population separate from embryonically produced OPCs. Note that OPCs continue cell divisions and increase in number while migrating toward widespread regions of the brain parenchyma (black arrows). (b) Stepwise differentiation of oligodendrocytes from neural stem cells (NSCs). Intermediate progenitor cell types in the oligodendrocyte lineage and their features and representative expressed/regulatory genes are schematically shown. For details, see text. Abbreviations: NSC, neural stem cell; OL, oligodendrocyte; OPC, oligodendrocyte progenitor cell; pre‐OL, pre‐myelinating oligodendrocyte. Others are same as in Figure
[ Normal View | Magnified View ]
Stepwise differentiation of neural stem cells (NSCs) into new neurons through intermediate cell types in the postnatal and adult brain. Intermediate progenitor cell types, and their features and representative regulatory transcription factor (TF) genes are schematically shown. Note that some TFs regulate NSCs in both the ventricular–subventricular zone (VZ–SVZ) and dentate gyrus (DG), whereas others operate in one stem niche but not in the other. For details, see text. Abbreviations: aNSCs, activated neural stem cells; NB, neuroblast; qNSCs, quiescent neural stem cells; TAP, transient amplifying progenitor. Others are the same as Figure
[ Normal View | Magnified View ]

Browse by Topic

Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease
Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration
Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches
Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion