Sox-2 is expressed by glial and progenitor cells and Pax-6 is expressed by neuroblasts in the human subventricular zone.
TL;DR: Investigation of the distribution and characterization of Sox-2 and Pax-6 in the human subventricular zone (SVZ) reveals that these TFs are differentially expressed in the adult human SVZ where Sox- 2 and Pax -6 specify a glial and neuronal fate, respectively.
About: This article is published in Experimental Neurology.The article was published on 2007-04-01. It has received 41 citations till now. The article focuses on the topics: Subventricular zone & Neurogenesis.
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TL;DR: Far from being a dormant layer, the SVZ responds to neurodegenerative disease in a way that makes it a potential target for therapeutic intervention.
Abstract: During brain development, one of the most important structures is the subventricular zone (SVZ), from which most neurons are generated. In adulthood the SVZ maintains a pool of progenitor cells that continuously replace neurons in the olfactory bulb. Neurodegenerative diseases induce a substantial upregulation or downregulation of SVZ progenitor cell proliferation, depending on the type of disorder. Far from being a dormant layer, the SVZ responds to neurodegenerative disease in a way that makes it a potential target for therapeutic intervention.
169 citations
TL;DR: A versatile protocol for fixation of post-mortem adult human brain tissue, storage of the tissue in a human brain bank, and immunohistochemical analysis in order to understand human brain functions in normal controls and in neuropathological conditions is established.
Abstract: One of the challenges for modern neuroscience is to understand the basis of coordinated neuronal function and networking in the human brain. Some of these questions can be addressed using low- and high-resolution imaging techniques on post-mortem human brain tissue. We have established a versatile protocol for fixation of post-mortem adult human brain tissue, storage of the tissue in a human brain bank, and immunohistochemical analysis in order to understand human brain functions in normal controls and in neuropathological conditions. The brains are fixed by perfusion through the internal carotid and basilar arteries to enhance the penetration of fixative throughout the brain, then blocked, postfixed, cryoprotected, snap-frozen and stored at -80 degrees C. Sections are processed for immunohistochemical single- or double-label staining and conventional-, electron- or confocal laser scanning-microscopy analysis. The results gained using this tissue and protocol are vital for determining the localization of neurochemicals throughout the human brain and to document the changes that occur in neurological diseases.
153 citations
TL;DR: A 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD is uncovered and indicates a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation.
Abstract: Background
Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive.
145 citations
TL;DR: The results indicate that Sox2 regulates the expression of key genes and pathways involved in GBM malignancy, in both cancer stemlike and differentiated cells, and maintains plasticity for bidirectional conversion between the two states, with significant clinical implications.
144 citations
TL;DR: Findings show that GFAP‐δ is expressed in an astrocytic subpopulation in the SVZ, the RMS and the OB, which is the first evidence thatGFAP‐ δ is specifically expressed in longterm quiescent cells in the human SVz, which are reminiscent of NSCs.
Abstract: A main neurogenic niche in the adult human brain is the subventricular zone (SVZ). Recent data suggest that the progenitors that are born in the human SVZ migrate via the rostral migratory stream (RMS) towards the olfactory bulb (OB), similar to what has been observed in other mammals. A subpopulation of astrocytes in the SVZ specifically expresses an assembly-compromised isoform of the intermediate filament protein glial fibrillary acidic protein (GFAP-delta). To further define the phenotype of these GFAP-delta expressing cells and to determine whether these cells are present throughout the human subventricular neurogenic system, we analysed SVZ, RMS and OB sections of 14 aged brain donors (ages 74-93). GFAP-delta was expressed in the SVZ along the ventricle, in the RMS and in the OB. The GFAP-delta cells in the SVZ co-expressed the neural stem cell (NSC) marker nestin and the cell proliferation markers proliferating cell nuclear antigen (PCNA) and Mcm2. Furthermore, BrdU retention was found in GFAP-delta positive cells in the SVZ. In the RMS, GFAP-delta was expressed in the glial net surrounding the neuroblasts. In the OB, GFAP-delta positive cells co-expressed PCNA. We also showed that GFAP-delta cells are present in neurosphere cultures that were derived from SVZ precursors, isolated postmortem from four brain donors (ages 63-91). Taken together, our findings show that GFAP-delta is expressed in an astrocytic subpopulation in the SVZ, the RMS and the OB. Importantly, we provide the first evidence that GFAP-delta is specifically expressed in longterm quiescent cells in the human SVZ, which are reminiscent of NSCs.
130 citations
Cites background from "Sox-2 is expressed by glial and pro..."
...The latter marker showed staining in both cell nuclei and in cytoplasm, which has been described before for the human brain (Baer et al., 2007)....
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References
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TL;DR: It is demonstrated that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans, indicating that the human hippocampus retains its ability to generate neurons throughout life.
Abstract: The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.
6,220 citations
TL;DR: It is shown that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone, and stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion.
Abstract: In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.
2,763 citations
TL;DR: It is shown here that constitutive expression of SOX2 inhibits neuronal differentiation and results in the maintenance of progenitor characteristics, and that SOXB1 signaling is both necessary and sufficient to maintain panneural properties of neural progenitors.
1,280 citations
TL;DR: Sox proteins perform their function in a complex interplay with other transcription factors in a manner highly dependent on cell type and promoter context, and exhibit a remarkable crosstalk and functional redundancy among each other.
Abstract: Sox proteins belong to the HMG box superfamily of DNA-binding proteins and are found throughout the animal kingdom. They are involved in the regulation of such diverse developmental processes as germ layer formation, organ development and cell type specifi-cation. Hence, deletion or mutation of Sox proteins often results in developmental defects and congenital disease in humans. Sox proteins perform their function in a complex interplay with other transcription factors in a manner highly dependent on cell type and promoter context. They exhibit a remarkable crosstalk and functional redundancy among each other.
874 citations
TL;DR: It is reported that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1–3) is a critical determinant of neurogenesis and the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.
Abstract: The generation of neurons from stem cells involves the activity of proneural basic helix-loop-helix (bHLH) proteins, but the mechanism by which these proteins irreversibly commit stem cells to neuronal differentiation is not known. Here we report that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1-3) is a critical determinant of neurogenesis. Using chick in ovo electroporation, we found that Sox1-3 transcription factors keep neural cells undifferentiated by counteracting the activity of proneural proteins. Conversely, the capacity of proneural bHLH proteins to direct neuronal differentiation critically depends on their ability to suppress Sox1-3 expression in CNS progenitors. These data suggest that the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.
801 citations