Biomedical Engineering Reference
In-Depth Information
6.3 Growth Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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6.4 Vascular Niches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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6.5 Transcription Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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7 Transit-Amplifying Type C Cells as a Glioma Cell-of-Origin . . . . . . . . . . . . . . . .
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8
Implications for Brain Tumor Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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9 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1 Development of Rodent Ventricular and Subventricular Zones
Neural stem cells, defined in vitro as cells that can self-renew and give rise to
multiple types of brain cells (Reynolds and Weiss 1992), persist in several
regions of the adult rodent brain, but most prominently in the subventricular
zone (SVZ), lining the lateral wall of the lateral ventricle. Among these two
germinal zones, the SVZ contains the largest reservoir of persistently dividing
cells. Progenitors in the SVZ, together with the subgranular zone (SGZ) of the
hippocampal dentate gyrus, continue to generate new neurons throughout life
(Alvarez-Buylla and Lim 2004).
The development and cellular composition of the rodent SVZ has been
described using a combination of cell fate mapping, immunohistochemistry,
and electron microscopy (Doetsch et al. 1997; Garcia-Verdugo et al. 1998;
Alvarez-Buylla et al. 2001; Merkle et al. 2004; Spassky et al. 2005). Although
historically it was believed that neuroepithelial cells in the early neural tube
produced two separate pools of committed glial and neuronal progenitors,
recent studies support a different model in which neuroepithelial cells either
produce or transform into radial glia (Kriegstein et al. 2006; Noctor et al.
2001). Additional data also confirm that neural stem cells are contained
within what was classically considered a macroglial lineage (i.e., neuroepithe-
lial cells
!
radial glia
!
astrocytes). Thus, soon after birth, radial glial cells
within the ventricular zone not only serve as progenitors for many glia
(including ependyma; Spassky et al. 2005) and young neurons (both radially
and tangentially migrating), but also give rise to the adult SVZ neural stem
cells that continue to produce neurons throughout adult life (Alvarez-Buylla
et al. 2001).
The cellular composition of the rodent SVZ is organized around slowly
dividing astrocyte-like neural stem cells known as type B cells (Doetsch et al.
1999). These cells give rise to actively proliferating type C cells (i.e., transit-
amplifying cells), which in turn give rise to immature neuroblasts, called
type A cells. In rodents, these neuroblasts are produced by a mosaic of
heterogeneous type B cells (Merkle et al. 2007) and migrate to the olfactory
bulb via tangentially oriented chains, differentiating into a variety of local
interneurons as they reach the olfactory bulb (Doetsch and Alvarez-Buylla
1996; Lois and Alvarez-Buylla 1994). These neuroblast chains are ensheathed
by the glial processes of type B cells and, in the anterior and dorsal SVZ, these
chains condense to form the rostral migratory stream (RMS; Lois et al. 1996).
