Sometimes, it’s useful to revisit reviews, and today’s a good day to describe what’s known about how neural progenitor cells maintain themselves in the adult brain. Neural progenitors afford the brain with its limited regenerative capacity – a capacity that medical doctors and scientists are trying to exploit, for treating damaged and degenerating components of the central nervous system (CNS).
These progenitors, which are what we call self-renewing, can also differentiate the critical cell types of the CNS. They are propagated in two restricted regions: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus subgranular zone (SGZ) of the hippocampus.
In a minireview in the March 2004 issue of Neuron, Alvarez-Buylla and Lim describe the apparent patterns of self-renewal and differentiation in the SVZ and SGZ.
Caption: Adult SVZ Neurogenesis(A) Coronal section through the adult mouse brain. Light blue shows the lateral ventricle (LV) space filled with cerebrospinal fluid. Boxed area is shown enlarged in (B).(B) Architecture of the SVZ. B cells (dark blue) are the astrocytes that are the SVZ stem cell and also serve as niche cells (see text for details). Some of the B cells contact the ventricle lumen and have a single cilium (shown). C cells (green) are rapidly dividing, transit-amplifying cells derived from the B cells. C cells give rise to A cells (red), neuroblasts that migrate to the olfactory bulb, where they become local interneurons. A blood vessel (BV, pink) is shown with a perivascular macrophage (dotted fill); a basal lamina (BL, yellow) extends from the BV and interdigitates extensively with the SVZ cells. Ciliated ependymal cells (gray) line the ventricle walls and have been shown to produce Noggin, which is important for this niche. Noggin, BMPs, Shh, Notch, TGFα, Eph/ephrins, and VEGF play roles in regulation of this neurogenic niche (see text).(C) SVZ lineage. C cells can behave as stem cells under the influence of excess EGF signaling.
Caption: Adult SGZ Neurogenesis(A) Coronal section through the adult mouse brain at the level of the hippocampus (HP). The dentate gyrus (DG, heavy dotted fill) is indicated by the arrow. The SGZ of the DG is shown enlarged in (B).(B) Architecture of the SGZ. Astrocytes (As, dark blue) give rise to progenitors (D cells, orange), which mature into new granule cells (red G cells). These newly born granule cells integrate into the DG granule cell layer (brown G cells). Blood vessels (BV, pink) are found close to the SGZ layer, and we propose that a perivascular basal lamina (BL, yellow dotted line) exists here similar to that found in the SVZ. Shh and VEGF regulate the SGZ niche in vivo (see text).(C) Lineage of the SGZ.
This represents one of the hot areas of stem cell research today – the eludication of the many factors and signals that influence the maintenance of such multipotent cell lineages, and the neurogenesis of such cells in the CNS. Enhancing such neurogenesis is one of the great hopes of modern biomedical research.
- Alvarez-Buylla A, Lim DA. For the long run: maintaining germinal niches in the adult brain.
Neuron. 2004 Mar 4;41(5):683-6. Pubmed