Trends in Neurosciences
Feature ReviewSpecial Issue: Circuit Development and RemodelingAdult neural stem cells stake their ground
Section snippets
Type B1 cells: a ‘displaced’ form of radial glia?
Consistent with their astrocytic morphology and ultrastructure, B1 cells express glial markers such as the glial-fibrillary acidic protein (GFAP), glutamate aspartate transporter (GLAST), and brain lipid binding protein (BLBP). Recent work indicates that B1 cells can exist in either a quiescent or activated state 10, 11. Interestingly, quiescent B1 cells do not appear to express Nestin, an intermediate filament protein that has long been considered to be a marker of NSCs. By contrast, activated
The regional identity of V–SVZ NSCs
NSCs located in geographically distinct regions of the ventricle walls produce different types of OB neurons 21, 22 (Figure 2). For instance, dorsal NSCs produce superficial granule cells (GCs) and anteriorly TH-positive periglomerular cells (PGCs), but few, if any, calbindin-positive PGCs. By contrast, ventral NSCs produce deep GCs and calbindin-positive, but not tyrosine hydroxylase (TH)-positive, periglomerular cells. Results from heterotopic grafting of NSCs (e.g., ventral NSCs transplanted
Activating the stem cell niche with blood vessels, ependyma, and neurons
Stem cells reside in a specialized microenvironment – or ‘niche’ – that contributes to the regulation of proliferation and progenitor cell differentiation. Similar to other stem cell populations 28, 29, 30, NSCs of the V–SVZ are regulated by a multitude of niche signaling pathways including SHH, Wnt, Notch, BMPs, and ephrins (see 4, 31 for more extensive review). The local vascular plexus also appears to be a source of important extrinsic signals for the regulation of V–SVZ progenitor cells.
Cell intrinsic signals for long-term and complex patterns in neurogenesis
SOX2 is a sequence-specific DNA binding transcription factor with many critical functions in a wide variety of cell populations throughout development [52]. How SOX2 performs such diverse roles in different cell types is not well understood, and recent studies of the V–SVZ lineage have shed light on this important and complex issue (Figure 3A). In the V–SVZ, SOX2 is expressed in essentially all V–SVZ cell types, including B1 cells [53]. B1 cells express the PRX1 homeobox transcription factor,
Epigenetic mechanisms for the maintenance of neurogenic competence
It has been suggested that B1 cells, like other stem cell populations, can self-renew and have the ability to generate multiple cell types. Conceptually, this cellular state of ‘stemness’ involves the expression of certain genes, repression of other specific loci, and transcriptional plasticity of genes necessary for lineage specification. Such complex patterns of transcriptional regulation involve the structure and function of chromatin. Chromatin states are regulated by both non-covalent and
The human brain V–SVZ
Recent studies have revealed intriguing differences between the rodent and human V–SVZ. In young children, the V–SVZ contains many DCX-positive cells, and there is a prominent RMS to the OB [95]. Furthermore, the brain of infants also has a medial migratory stream of young neurons from the V–SVZ to the medial prefrontal cortex, which is a migratory path not evident in the rodent brain. After 18 months of age, few DCX-positive cells are observed in the human V–SVZ. Instead, there is a prominent
Concluding remarks
Over the past 2 decades, in vivo and in vitro studies of the V–SVZ have revealed the experimental advantages of studying a germinal niche that remains active throughout adult life. As discussed above, neurogenesis in the V–SVZ involves an intriguing interplay between niche signals including epithelial and vascular-derived signals, as well as activity-dependent neurotransmitters. Furthermore, the maintenance of long-term neurogenesis and regional NSC specification has been discovered to involve
Acknowledgments
This work was supported by NIH grant DP2-OD006505, VA grant 1I01 BX000252, a Sontag Foundation Award, and a generous gift from the Shurl and Kay Curci Foundation to D.A.L. A.A.B is the Heather and Melanie Muss Endowed Chair and is supported by NIH grants HD032116, NS28478, and a generous gift from the J.G. Bowes Foundation. We thank Joseph Elsbernd and Luis Fuentealba for their helpful edits and comments on the manuscript and Ken Probst for illustrations.
Glossary
- Regional identity
- the developmental specialization of precursor cells based on their physical location.
- Epigenetics
- the study of heritable patterns of gene expression that do not involve changes to the DNA sequence.
- Chromatin
- the dynamic polymer of DNA and histone proteins. The nucleosome – approximately 146 bp of DNA wrapped approximately twice around an octamer of the four core histone proteins (H2A, H2B, H3, H4) – is the basic subunit of chromatin. Chromatin can undergo non-covalent and covalent
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