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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies using retroviral labeling of subventricular zone (SVZ) progenitors in vivo in neonatal rats have directly demonstrated the generation of both astrocytes and oligodendrocytes from these progenitors. In the present study, we used a recombinant retroviral vector encoding beta-galactosidase, and analyzed brains within the first week after retroviral injection to trace the early routes that SVZ cells take as they migrate into white matter and cortex and characterized the early morphological and antigenic changes that accompanied their differentiation. SVZ cells follow specifically definable migratory routes as they colonize the cortex and subcortical white matter. Glial progenitors do not populate the cortex in a systematic, laminar fashion, as do neuroblasts. The abundance of labeled progenitors in radial arrangements and the close apposition of many immature cells to vimentin+ radial glial processes, suggest that glial progenitors migrate along radial glia. Labeled SVZ cells, which displayed a simple, unipolar or bipolar morphology, lacked detectable vimentin and nestin intermediate filaments. Similarly, beta-galactosidase-positive cells in white matter lacked these filaments. In contrast, labeled, multipolar cells in the cortex, and a few of the immature-appearing cortical cells expressed nestin and vimentin. At these early time points, GFAP was not detected in beta-galactosidase-labeled cells. Multipolar cells in cortex frequently displayed processes extending toward and contacting blood vessels. These observations suggest that the expression of nestin and vimentin occurs after progenitors emigrate from the SVZ and that filament expression and contact with blood vessels represent an early stage of astrocyte differentiation.
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PMID:Early patterns of migration, morphogenesis, and intermediate filament expression of subventricular zone cells in the postnatal rat forebrain. 747 78

Embryonic Purkinje cells (PCs) from cerebellar primordia grafted in adult pcd mutant cerebellum replace missing PCs of the host, and become synaptically integrated into the defective cerebellar circuit. This process of neuronal replacement starts with the invasion of grafted PCs into the host cerebellum, and their radial migration through its molecular layer. The present study is aimed at determining whether the glial axes for this migration are embryonic radial glial cells that comigrate with the grafted PCs, or adult Bergmann fibers of the host, transiently reexpressing the molecular cues needed for their guidance of the migration. Transplants from a transgenic mouse line (Krox-20/lacZ14) in which Bergmann fibers could be identified by lacZ expression reveal that, despite the presence of X-gal-stained Bergmann fibers in the graft remnants and of grafted PCs in the host molecular layer, all Bergmann fibers in the host cerebellum lack of beta-galactosidase activity. Thus, these migratory axes belong to the host, not to the donor. Transplants from normal isogenic mouse embryos show that during the radial migration of grafted PCs (7 d after grafting) the involved host Bergmann fibers reexpress nestin (identified with monoclonal antibody Rat-401 immunostaining), normally expressed only by immature Bergmann fibers. Five days later, when grafted PCs have arrested their migration, host Bergmann fibers again become Rat-401 negative. These results indicate that embryonic PCs can trigger in adult cerebellum the molecular changes necessary for their own migration and ultimate synaptic integration in the host cortical circuitry.
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PMID:Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells. 828 29

An efficient gene trap strategy was devised for identifying the genes that are expressed in the mouse developing nervous system. Mouse embryonic stem (ES) cell lines that carried independent integrations of a gene trap vector, pSneolN/acZA, were allowed to differentiate in a suspension culture system. To select cells containing neurons, astrocytes or neuron-glia precursors, cell lines were immunohistochemically examined with antibodies against neuron-specific proteins (neurofilament protein 150 kD and microtubule associated protein 2), glial fibrillary acidic protein or nestin. Three cell clones (GT3-8, 11 and 12) were immunoreactive to either of the antibodies employed and at the same time positive for beta-galactosidase activity. When chimeric embryos were generated by the use of the above 3 cell lines, some cells in their nervous system showed X-gal staining. Thus the major advantage of the present gene trap method lies in its prescreening step of manipulated ES cells prior to generation of chimeric animals. This method holds promise as a useful tool for investigating the genes involved in the development of the nervous system.
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PMID:A gene trap strategy for identifying the gene expressed in the embryonic nervous system. 876 26

Brain disorders induced by congenital cytomegalovirus (CMV) infection may appear at a later time after birth as a consequence of persistent infection and/or the activation of a latent infection of the neural cells. We have analyzed the infection dynamics of the neural cells in the neonatal mouse brains infected with murine CMV (MCMV) in the late stage of gestation. First we prepared a rat monoclonal antibody to the major immediate-early (IE)-89K antigen and then used the antibody for comparison of the expression of early and late viral genes in the developing mouse brains. The cells expressing the IE-89K antigen were mostly localized in the ventricular and subventricular zones and were preferentially double stained with anti-glial fibrillary acidic protein and anti-nestin antibodies. In contrast, the cells expressing the early nuclear antigen, detected by the monoclonal antibody D5, were diffusely distributed in the cortex and the hippocampus and were mostly double labeled with anti-neuron-specific enolase antibody. In neonatal mouse brains infected congenitally with recombinant MCMV, which expressed lacZ as a late gene, the number of the early nuclear antigen-positive cells was much higher than that of the beta-galactosidase-expressing cells, the number of which was almost the same as that of the IE-89K antigen-positive cells. In addition, the distribution of viral DNA-rich cells detected by DNA-DNA hybridization was similar to that of the IE-89K antigen-positive cells. These results suggest that CMV may persistently infect neuronal cells, whereas lytic infection may preferentially occur in the glial cells in the developing brain.
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PMID:Differential expression of the immediate-early and early antigens in neuronal and glial cells of developing mouse brains infected with murine cytomegalovirus. 935 59

Neural progenitor cell populations responsive to epidermal growth factor (EGF) have been shown to have proliferative potential and give rise to neurons, astrocytes, and oligodendrocytes. We have characterized EGF-responsive neural progenitor cells that give rise to bilineage neuronal/glial colonies (colony-forming unit neuron-glia; CFU-NeGl) and unilineage neuronal colonies (CFU-Ne). Clonality was confirmed utilizing mixtures of brain cells from Balb/c and ROSA26 (transgenic for beta-galactosidase) mice. With a few exceptions, colonies showed either all blue cells or all clear cells after staining with X-Gal. Clonal growth was analyzed after 10-11 days in relation to cell density by determining colony size and plating efficiency. Growth was density dependent (no growth below 10,000 cell/ml) and thus single cell cloning was not accomplished. An average plating efficiency of 4% was found for EGF-responsive neural cells derived from day 15-18 murine embryos when cultured at 12,500 to 200,000 cells/ml. Similar results were obtained with 1-day-old postnatal neural cells. When colonies were categorized by size, the relative number of colonies over 50 cells appeared to be maximum at 50,000 plated cells/ml. After 11 days in culture, 94, 96, and 78% of the colonies contained cells that expressed nestin, neurofilament, and GFAP, respectively. Double-label experiments revealed that > 62% of the colonies contained both GFAP and neurofilament expressing cells. These studies establish the existence of at least two populations of clonal neural progenitors: CFU-Ne and CFU-NeGl in fetal and postnatal murine brain.
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PMID:In vitro cell density-dependent clonal growth of EGF-responsive murine neural progenitor cells under serum-free conditions. 939 57

In this report, we have examined the relationship between the onset of neuronal gene transcription and neuronal development by characterizing expression of the early panneuronal Talpha1 alpha-tubulin promoter in developing neurons. In the peripheral nervous system, detectable expression of a beta-galactosidase transgene driven by the Talpha1 promoter (Talpha1:nlacZ) was coincident with neuronal birth dates, with the exception of sympathetic neuroblasts, which expressed the transgene prior to terminal mitosis. Similarly, in the central nervous system, the onset of beta-galactosidase expression was coincident with neuronal birth dates in most identifiable populations of central neurons. A small subpopulation of transgene-positive cells localized to ventricular zones, but the vast majority was observed in locations consistent with their identification as migrating and/or differentiating neurons. To determine more precisely the temporal relationship between transgene expression and terminal mitosis, we analyzed cultures of cortical progenitors that become postmitotic neurons in vitro. When initially plated, the vast majority of cells consisted of dividing, nestin-positive progenitors. Neurons differentiated from these progenitors as early as 1 day in vitro, as indicated by immunostaining for betaIII-tubulin, a neuron-specific tubulin isotype that is turned on shortly after terminal mitosis. Double-labeling studies showed that Talpha1:nlacZ expression was detectable in the same cells and at approximately the same time as was betaIII-tubulin, indicating that detectable transcription of the Talpha1 alpha-tubulin promoter commences at the time of terminal mitosis, at least in culture. This promoter, therefore, provides a valuable tool for genetic manipulation of early developing neurons in transgenic mice.
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PMID:Early induction of Talpha1 alpha-tubulin transcription in neurons of the developing nervous system. 1002 95

For glioma- and glioblastoma-specific gene expression, we utilized a nestin regulatory element whose activity was evaluated by the reporter gene lacZ. Nestin is a 38-kDa intermediate filament protein, and is expressed specifically in the neuroepithelial stem cells. Nestin is detected in gliomas and glioblastomas, but not in normal brain tissue. We constructed a nestin gene regulator by placing nestin's second intron before the 5' upstream region (2iNP). To obtain enhanced expression of this tissue-specific regulator, we utilized the adenovirus double-infection method with a Cre-loxP on/off switching system. We constructed a 'regulator' vector, Ax2iNPNCre, which expresses Cre recombinase under the control of the nestin regulatory element, 2iNP. A 'reporter' vector, AxCALNLNZK, expresses lacZ under the control of a strong CAG promoter when the stuffer sequence has been removed by Cre recombinase at a pair of loxP sites. We used seven human glioma/glioblastoma cell lines: U251, KG-1C, NGM5, U87 MG, LN-Z308, NP-2 and T98G. Of these, nestin was expressed highly in U251 and KG-1C, less in NGM5, and undetectably in the other four lines. With the use of the two adenovirus vectors, we found X-gal staining and high nestin regulator-promoted beta-galactosidase activities in four of the seven glioma/glioblastoma cell lines. Staining was strong in U251, KG-1C and NGM5, and less in U87 MG. LacZ expression was nearly undetectable in the non-glioma cell line, HeLa, but a little in COS-7. The adenovirus double-infection method, which uses a nestin regulator, is applicable for glioma/glioblastoma-specific expression.
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PMID:Glioma/glioblastoma-specific adenoviral gene expression using the nestin gene regulator. 1080 92

To clarify the lineage relationship between cells that express the neural stem cell marker nestin and endocrine cells of the pancreas, we analyzed offspring of a cross between mice carrying a nestin promoter/enhancer-driven cre-recombinase (Nestin-cre) and C57BL/6J-Gtrosa26(tm1Sor) mice that carry a loxP-disrupted beta-galactosidase gene (Rosa26). In nestin-cre(+/tg);R26R(loxP/+) embryos, cre-recombinase was detected in association with nestin-positive cells in the pancreatic mesenchyme with some of the nestin-positive cells lining vascular channels. In postnatal mice, pancreatic beta-galactosidase expression was restricted to vascular endothelial cells of the islet and a subset of cells in the muscularis of arteries in a distribution identical to endogenous nestin expression. Ex vivo explants of mouse pancreatic ducts grew dense cultures that costained for nestin and beta-galactosidase, demonstrating recombination in vitro. The cultures could be differentiated into complex stereotypic structures that contain nestin- and insulin-expressing cells. Nestin-cre(+/tg);R26R(loxP/+)-derived duct cultures showed that insulin-positive cells were negative for beta-galactosidase. These results indicate that both in vivo and in vitro pancreatic endocrine cells arise independently of nestin-positive precursors. The apparent vascular nature of the nestin-positive cell population and the close association with endocrine cells suggest that nestin-positive cells play an important role in the growth and maintenance of the islet.
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PMID:Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet. 1451 33

Expression of nestin has been suggested to be a characteristic of pancreatic islet stem cells. To determine whether nestin is indeed expressed in such putative cells during embryonic development, or in the adult pancreas after injury, we performed a cell lineage analysis using two independent lines of transgenic mice encoding Cre recombinase under the control of rat nestin cis-regulatory sequences, each crossed with loxP-bearing R26R mice. F1 animals produced the reporter molecule beta-galactosidase only upon Cre-mediated recombination, thus solely in cells using (or having used) the transgenic nestin promoter. In early pancreatic primordia, beta-galactosidase was observed in mesenchymal and epithelial cells. At later developmental stages or in adults, vast clusters of acinar cells and few ductal cells were labeled, in addition to fibroblasts and vascular cells, but no endocrine cells were tagged by beta-galactosidase. This correlated with the transient expression, observed with an anti-nestin antibody, of endogenous nestin in about 5% of epithelial cells during development (whether in cord-forming arrangements or in nascent acini), and in vascular and mesenchymal structures. After partial pancreatectomy, there was a transient increase of the number of anti-nestin-labeled endothelial cells, but again, no endocrine cells bore beta-galactosidase. Together, these findings show that nestin is expressed in the pancreatic exocrine cell lineage, and suggest that consistent nestin expression is not a major feature of islet endocrine progenitor cells.
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PMID:Nestin expression in pancreatic exocrine cell lineages. 1470 95

Nestin, an intermediate filament protein, is widely used as stem cell marker. Nestin has been shown to interact with other cytoskeleton proteins, suggesting a role in regulating cellular cytoskeletal structure. These studies examined renal nestin localization and developmental expression in mice. In developing kidney, anti-nestin antibody revealed strong immunoreactivity in vascular cleft of the S-shaped body and vascular tuft of capillary loop-stage glomerulus. The nestin-positive structures also were labeled by endothelial cell markers FLK1 and CD31 in immature glomeruli. Nestin was not detected in epithelial cells of immature glomeruli. In contrast, in mature glomerular, nestin immunoreactivity was observed only outside laminin-positive glomerular basement membrane, and co-localized with nephrin, consistent with podocyte nestin expression. In adult kidney, podocytes were the only cells that exhibited persistent nestin expression. Nestin was not detected in ureteric bud and its derivatives throughout renal development. Cell lineage studies, using a nestin promoter-driven Cre mouse and a ROSA26 reporter mouse, showed a strong beta-galactosidase activity in intermediate mesoderm in an embryonic day 10 embryo and all of the structures except those that were derived from ureteric bud in embryonic kidney through adult kidney. These studies show that nestin is expressed in progenitors of glomerular endothelial cells and renal progenitors that are derived from metanephric mesenchyme. In the adult kidney, nestin expression is restricted to differentiated podocytes, suggesting that nestin could play an important role in maintaining the structural integrity of the podocytes.
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PMID:Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes. 1657 84


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