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J de Vellis

Publications and source records attributed to J de Vellis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Id1, Id2, and Id3 gene expression in neural cells during development.

Id1, Id2, and Id3 mRNA are expressed mainly in the proliferating ependymal cell zone of the mouse brain during embryogenesis. In this study, the expression pattern and cell phenotypes of the Id family mRNA were examined in postnatal and adult rat brain. The expression of Idl and Id3 mRNA in rat brain was observed in the cortex layer 1, corpus callosum, ventricular/subventricular zone (VZ/ SVZ), and the CA1-4 layers of the hippocampus at postnatal day 1 (P1) through P14, whereby it declined at 2 months. In general, the developmental pattern of Idl mRNA coincided with the pattern observed for Id3 mRNA. Similar to Id1 and Id3, Id2 mRNA was highly expressed in the corpus callosum, VZ/SVZ, and the hippocampus. Examination of Id2 mRNA revealed high levels in the cortex and caudate putamen at P1 through P14, whereas a decline was observed in its expression in the adult cortex. In P5 rat cerebellum, all Id mRNA examined were found in the internal granular cell layers; however, at this time point, only Id2 mRNA expression was detected in the differentiating zone of the external granular cell layers, preferentially localizing to adult Purkinje cells. Furthermore, only Id2 mRNA expression in brain was observed in NF+ neurons at P5. Examination of S100alpha+ and GFAP+ astrocytes, revealed the presence of all three mRNAs, whereas the expression of Id2 and Id3 mRNA was absent in 04+ immature oligodendrocytes. These data suggest that the spatial and temporal kinetic patterns during development, as well as cellular specificity, of the Id gene family may play a critical role in neural precursor cell proliferation and cell divergence.

Animals↗
PubMed1998

Expression of the antioxidant gene NKEF in the central nervous system.

Free radicals and the oxidative stress they impose can cause serious injury in the nervous system and contribute to pathology associated with a wide variety of degenerative and traumatic disorders. In this study, we examined the expression of an antioxidant defense gene, nkef, in human tissue and isolated populations of rat brain cells using Western and Northern blot analysis. NKEF protein was expressed in human brain, liver, kidney, muscle, and lung. The human endothelial cell line ECV expressed a 25-kDa band in addition to the 22-kDa band normally observed. In the central nervous system, a 22-kDa NKEF band was present in cortical gray and white matter, hippocampus, cerebellum, and spinal cord in roughly similar amounts. Expression of NKEF-A and NKEF-B subtypes was evaluated by Northern analysis of cultured cell types from embryonic rat brain. Astrocyte and microglia expressed both 22- and 25-kDa bands, whereas cortical neurons and oligodendrocytes contained only the 22-kDa protein band. Northern blot analysis of these cell types revealed low levels of NKEF-A message in neurons and oligodendrocytes, and relatively low levels of NKEF-B in microglia. Differential expression of these antioxidant defense genes may contribute to the selective vulnerability of brain cell types to specific kinds of oxidative stress.

Animals↗
PubMed1997

Transplantation of CG4 oligodendrocyte progenitor cells in the myelin-deficient rat brain results in myelination of axons and enhanced oligodendroglial markers.

Transplantation of oligodendrocyte (Ol) progenitor cells into the central nervous system is a promising approach for the treatment of myelin disorders. This approach requires providing adequate numbers of healthy cells with myelinating potential. We recently showed the successful transplantation of Ol progenitors into the myelin-deficient (md) rat brain. In the present work, CG4 cells, a cell line with properties of Ol progenitors, were labeled with fast blue and grafted into P3-P5 pups born to carrier mothers. Examination of host brains 2 weeks posttransplant indicated that CG4 cells display a much more extensive migration capacity than their wild-type counterparts. These cells synthesized myelin components. In addition, ultrastructural analysis showed myelin formation along axons of md hosts in various brain regions, including corpus callosum, cerebellum, and brainstem. Furthermore, in situ hybridization studies performed on sagittal sections revealed extensive expression of transferrin-mRNA within the md host parenchyma. The high survival and functional features displayed by CG4 cells after transplantation, together with their striking wide distribution within the host parenchyma, as assessed by the presence of myelinated fibers in mutant hosts, emphasizes the importance of using highly motile and proliferative Ol progenitor cells. Strategies to improve the condition and life span of md rat pups are currently under investigation.

Animals↗
PubMed1997

Transferrin is an early marker of hepatic differentiation, and its expression correlates with the postnatal development of oligodendrocytes in mice.

Transferrin (Tf), the iron transport protein, is essential for the growth and differentiation of cells. Therefore, it provides an excellent model to analyze the regulatory mechanisms controlling the expression of a eukaryotic gene in different cell types and during fetal and adult life. In this study, the tissue-specific and developmental regulation of the Tf gene in vivo were analyzed. Human Tf mRNA was detected mainly in fetal and adult liver. A weaker expression was observed in adult and fetal brain and in fetal spleen. By in situ hybridization the presence of mouse Tf mRNA was detected in the hepatic primordia. This is the first observation pointing out Tf as an early marker of hepatic differentiation, prior to the formation of the liver. Thus, TF may be an important tool to follow the hepatic specification of the gut endoderm. Mouse Tf mRNA was also detected in the liver bud and subsequently in the liver throughout fetal life, and in newborn and adult animals. No expression of the Tf gene was observed in the mouse fetal central nervous system (CNS). In contrast, Tf mRNA was detected from the 5th day after birth in the derivatives of the caudal part of the neural tube and subsequently in the derivatives of the rhomboencephalon and that of the prosencephalon. These results indicate that Tf gene expression correlates with the postnatal development of oligodendrocytes in the mouse CNS. To test whether the control elements of the human gene previously found in ex vivo experiments were also active in vivo during fetal and adult life, we fused the -4000/+395' flanking region of the human gene to the coding region of the lacZ gene and generated transgenic mice. The expression of the reporter gene during development was analyzed.

Aging↗
PubMed1997

Glial- and fat-specific expression of the rat glycerol phosphate dehydrogenase-luciferase fusion gene in transgenic mice.

Glycerol phosphate dehydrogenase (GPDH) is a metabolic enzyme that catalyzes the conversion of dihydroxyacetone phosphate to glycerol-3-phosphate. It provides phospholipid precursors for lipid biosynthesis and energy metabolism. In the brain, GPDH enzymatic activity, protein, mRNA are exclusively associated with oligodendroglial and Bergmann glial cells. Expression of GPDH in the brain increases dramatically during the active period of myelination, and is regulated by extracellular signals. In an effort to understand the mechanism that confers glial-specific expression of GPDH, we have examined the role of the 5' flanking sequence of the rat GPDH gene in conferring cell-specific expression of reporter gene in transgenic mice. Luciferase reporter constructs containing either the full-length GPDH 5' flanking region (p4.3), or a distally truncated version (p2.6), were injected into mouse zygotes. Three independent lines of transgenic mice containing the p4.3, and seven lines of mice containing the p2.6 constructs, were analyzed. Luciferase enzyme activity was detectable only in brain and fat, not in other GPDH-positive organs such as liver, muscle, and kidney. Both the full-length and the distally deleted transgenes were expressed similarly in these two organs, indicating that the distal portion of the 5' flanking region was not required for brain- and fat-specific expression. Immunocytochemical analyses revealed that luciferase immunoreactivity colocalized with glial fibrillary acidic protein (GFAP)-positive Bergmann glia in the cerebellum, and myelin basic protein (MBP)-positive oligodendroglia in the cerebral cortex and the brainstem. Results here suggest that the rat GPDH 5' flanking region directs glial-specific expression of GPDH transcription in the brain, and provide a good model for analyses of changes in glial metabolism in response to extracellular perturbations in vivo.

Adipose Tissue↗
PubMed1997

CNTF induces GFAP in a S-100 alpha brain cell population: the pattern of CNTF-alpha R suggests an indirect mode of action.

In a recent report, we demonstrated that intracerebral injections of the pleiotropic cytokine, ciliary neurotrophic factor (CNTF), into developing postnatal rats evoked a severe inflammatory response as determined by the appearance of reactive astrocytes and activated microglia. Considering the likely involvement of CNTF in the injury response, we felt it was important to further understand the role of CNTF in the developing rat CNS. In this study, we examined the responsiveness of other cell populations to intracerebral injections of CNTF. We report that CNTF increases glial fibrillary acidic protein (GFAP), while having no appreciable effect on the levels of other intermediate filaments including vimentin and neurofilament. Moreover, CNTF did not affect the expression of the mature oligodendrocyte gene, myelin basic protein. These results suggest that CNTF is highly specific in its regulation of GFAP. In our previous study, we showed CNTF to increase GFAP in a cell population that already exists in the CNS parenchyma. To determine the origin of the CNTF-induced reactive astrocytes, therefore, we have utilized a technique of combined in situ hybridization and immunocytochemistry. To examine the possibility that CNTF acts on oligodendrocyte precursors to give rise to reactive astrocytes, the platelet-derived growth factor alpha receptor (PDGF-alpha R) was utilized as a riboprobe in conjunction with an antibody to GFAP. Examination of CNTF-induced GFAP+ astrocytes revealed no colocalization with PDGF-alpha R mRNA. In contrast, when we utilized an S100 alpha antibody recognizing a calcium binding protein in immature astrocytes, we found colocalization of S100 alpha and GFAP mRNA. These data suggest that CNTF induces an upregulation of GFAP in immature S100 alpha + astrocytes. Examination of the CNTF-alpha receptor mRNA revealed no change in expression following CNTF treatment. Unexpectedly, however, the CNTF-induced astrogliotic response appears to be indirect since the CNTF-alpha receptor was solely expressed by neurons in the cytokine-treated animals.

Animals↗
PubMed1997

Expression and functional role of the Id HLH family in cultured astrocytes.

The Id family of helix-loop-helix factors (Id1, Id2, and Id3) expressed in many types of cells has been reported to negatively regulate myoblast differentiation and is required for G1/S progression of arrested fibroblasts. Our previous studies have indicated that Id1, Id2, and Id3 mRNA expression appear in the subventricular zone of 1-day-old rat brains. At later ages, Id3 mRNA was only expressed in astrocytes. We now report that Id1 and Id3 mRNA expression increased in astrocytes during the first hour of serum stimulation. Subsequently, the Id1 and Id3 mRNA levels gradually declined to basal level as observed in cultures without serum stimulation. However, there was no significant difference in Id2 mRNA expression between serum-treated and control astrocyte cultures within 1 h of serum induction. In addition, a strong nuclear immunostaining for Id2 and Id3 proteins was observed 24 h after serum stimulation. This observation is consistent with our results that show an increase in Id2 and Id3 protein levels following 24 h serum induction. Furthermore, DNA synthesis in FCS-stimulated astrocytes was blocked by antisense oligonucleotides against Id3 mRNA. The addition of Id3 antisense oligonucleotides caused approximately 50% reduction in Id3 mRNA and protein levels when compared to that in sense-treated cultures. The results indicate that the inhibition of DNA synthesis in FCS-stimulated astrocytes is due to a decrease in Id3 levels by the antisense. These observations suggest that Id3 may play an important role in the regulation of astrocyte proliferation.

Animals↗
PubMed1997

Ciliary neurotrophic factor activates JAK/Stat signal transduction cascade and induces transcriptional expression of glial fibrillary acidic protein in glial cells.

In recent reports, ciliary neurotrophic factor (CNTF) has been implicated as an injury factor involved in regulating astrogliosis in the CNS. In this study, we used a rat oligodendroglial progenitor cell line that is highly responsive to CNTF to examine CNTF-induced alterations that may play a role in activation of the glial fibrillary acidic protein (GFAP) gene. We determined that CNTF induces the transient translocation of Stat1 alpha/p91 to the nucleus. This nuclear translocation was followed by GFAP promoter activation and an up-regulation of GFAP mRNA and protein. Level of CNTF-alpha receptor mRNA, however, were unaffected by addition of the ligand. Transfection studies using an upstream 5'-flanking, 1.9-kb rat GFAP promoter linked to a luciferase reporter gene revealed CNTF-induced transcriptional activation within 1 h of ligand exposure. Moreover, serial-deleted constructs identified a distal (-1,857 to -1,546 bp) and a proximal (-384 to -106 bp) region as being important for CNTF-induced GFAP promoter activation. These two regions showed a strong degree of overlap for CNTF- and serum-induced activation of the GFAP gene. Analysis of the two regions revealed several cis-elements that are thought to be involved in GFAP regulation and/or the regulation of other genes by members of the interleukin-6 family of cytokines. Moreover, we are the first to report the presence of several putative CNTF-responsive elements within our identified distal and proximal regions in the GFAP gene promoter.

Acute-Phase Proteins↗
PubMed1997

A neural-specific hypomethylated domain in the 5' flanking region of the glial fibrillary acidic protein gene.

In the present study we examined the methylation status of the glial fibrillary acidic protein (GFAP) gene promoter, analyzing various CG sites in both the human and rat gene in GFAP-expressing and nonexpressing tissues. Moreover, we studied the methylation of specific CG sites in different rat brain areas during postnatal development, in cell cultures highly enriched in specific neural- or non-neural-cell types (fibroblasts), and in human gliomas. The obtained results do not support a simple correlation between demethylation and expression of the GFAP gene but help to identify a cluster of CG sites in the 5'flanking region (from -1176 to -1471 in the rat) that are hypomethylated in neural cell types and localized in a region highly conserved between rat, mouse and human GFAP promoters. Neural-specific hypomethylation of this conserved zone can be observed also in the human GFAP gene both in normal brain tissue and neoplastic glial cells. A higher demethylation of the -1176 site at early stage of postnatal life was observed in specific rat brain areas, such as hippocampus and cerebellum. The most dramatic differences were observed in the cerebellum where a peak of demethylation of the -1176 site was detected at 15 days of postnatal life, followed by an intense remethylation of this site. Results of experiments in the CG4 glial progenitor cell line showed that demethylation of the -1176 site is already established before transcriptional activation of the GFAP gene. Moreover, results of experiments in primary cell cultures show that in neuronal cell types, such as cerebellar granule cells and embryonic cerebral hemisphere neurons, the level of demethylation of the -1176 site is comparable to that observed in cultured astrocytes. In contrast a high level of methylation can be observed in cultured non-neural cell types (fibroblasts). Such neural-specific hypomethylation could be established in a very early stage in the progression along the neural cell lineage and could play a role in maintaining a local open chromatin conformation which is then necessary to allow the interaction with specific regulatory factors present in astroglial cells.

Animals↗
PubMed1996

Evidence for neuronal regulation of oligodendrocyte development: cellular localization of platelet-derived growth factor alpha receptor and A-chain mRNA during cerebral cortex development in the rat.

Oligodendrocyte responses in vitro to platelet-derived growth factor (PDGF) include proliferation, survival, migration, and changes in cell morphology and molecular expression. Studies of mixed glial cultures established that astrocytes secrete PDGF; thus astrocytes are considered to be key regulators of oligodendrocyte development in vitro. We previously demonstrated PDGF alpha receptor mRNA expression by oligodendrocyte progenitors and preoligodendrocytes during postnatal development of rat cerebral cortex. In the present study, we have mapped the spatial and temporal expression of PDGF A-chain ligand mRNA and alpha receptor mRNA to determine if the cell-cell interactions that form the basis for PDGF regulation of oligodendrocyte development in vitro are also present in vivo. By in situ hybridization (ISH) we demonstrate that at embryonic day 17 (E17) cells expressing receptor mRNA (PDGFR alpha +) are initially in the subventricular zone, at a distance from cells expressing ligand mRNA (PDGF+) in the cortical plate. By E20 PDGFR alpha + cells are found throughout the corpus callosum and cortical gray matter. PDGF+ cells are restricted to the cortical plate prenatally and only appeared in the corpus callosum postnatally. Combined immunocytochemistry and ISH demonstrated the PDGF+ cells colocalized with neurofilament, but not with GFAP. These data establish that PDGF is expressed by neurons during PDGFR alpha + oligodendrocyte progenitor migration from the subventricular zone to the corpus callosum and gray matter. Furthermore, neurons continue to express PDGF during the generation and differentiation of appropriate numbers of oligodendrocytes needed to myelinate axons as the nervous system matures.

Animals↗
PubMed1996

Neurotrophin activates signal transduction in oligodendroglial cells: expression of functional TrkC receptor isoforms.

The role of the NT-3 has been implicated in the survival of progenitor oligodendrocytes in culture. The object of this study was to investigate the expression of the TrkC receptor and its responsiveness in glial cells. We report the expression of two TrkC receptor isoforms in rat primary oligodendrocyte cultures, a glial progenitor cell line, CG-4, and in C6 glioma cells. The reverse transcription-polymerase chain reaction-aided amplification of glial trkC with specific primers from the kinase domain, followed by its cloning and sequencing, shows the presence of two trkC transcripts. The sequence of one of the transcripts is homologous to a previously identified trkC isoform which encodes a functional receptor. The other transcript contains a 42-bp insert in the kinase domain. A Western blot of CG-4 and C6 probed with antibody to a TrkC revealed the presence of gp145-kDa protein band. The investigations revealed a rapid autophosphorylation of gp145TrkC in CG-4 and C6 cells in the presence of its specific ligand, NT-3. Furthermore, K252a, a neurotrophin-specific inhibitor, abolishes the NT-3-mediated receptor autophosphorylation. We also examined other NT-3-dependent phosphorylation of cellular substrates in oligodendroglial cells. Interestingly, we observed phosphorylation of phospholipase C gamma-1 in CG-4 and C6 cells, and phosphorylation of phosphatidylinositol 3-kinase in C6 cells in the presence of NT-3. Both the NT-mediated phosphorylation of phospholipase C gamma-1 and phosphorylation of phosphatidylinositol 3-kinase are blocked in the presence of K252a. The detection of the NT-3-mediated early signal transduction events demonstrates that TrkC receptor exhibits NT-3-mediated intracellular response in oligodendroglial cells.

Animals↗
PubMed1996

Hippocampal responses to corticosterone and stress, one of which is the 35,000 M(r) protein, glycerol phosphate dehydrogenase.

Previously, the synthesis of a hippocampal 35,000 M(r) protein increased in response to glucocorticoid treatment and a variety of stressors. We now show by immunoprecipitation that this cytosolic protein is glycerol 3-phosphate dehydrogenase (E.C.1.1.1.8; GPDH). In addition, four polypeptides encoded by glucocorticoid-induced mRNAs co-migrated with hippocampal protein synthetic products on two-dimensional polyacrylamide gels, including 35,000 M(r) protein of approximately pl 6.3, that had previously been identified as GPDH by hybrid-selection with a GPDH cDNA clone. The 35,000 M(r) in vitro translation product was also immunoprecipitated with the GPDH antibody. Using radiolabeled hippocampal slices and two-dimensional gel analysis, a 35,000 M(r) polypeptide of approximately pl 6.4 increased five-fold after 30 min of intermittent tail-shock. This protein was found predominantly in the 20,000 x g pellet and did not immunoprecipitate with the GPDH antibody. However, a 35,000 M(r) polypeptide was also found in the cytosol as a minor component after stress, which did immunoprecipitate with the GPDH antibody. Therefore, there are at least two shock-induced 35,000 M(r) proteins, one of which is GPDH. These results establish that increases in GPDH mRNA prevalence and protein synthesis occur in response to both glucocorticoids and stress in the adult rat hippocampus. Based on the increased enzyme activity seen in the nervous system in response to glucocorticoids, dietary restriction, and nerve injury, the induction of GPDH may have functional consequences in cellular adaptation to stress.

Animals↗
PubMed1995

CNTF regulation of astrogliosis and the activation of microglia in the developing rat central nervous system.

In response to physical or chemical brain injury, the mammalian central nervous system (CNS) often reacts by evoking astrogliosis. The most prominent feature describing this state is an upregulation of glial fibrillary acidic protein (GFAP). The agent(s) responsible for inducing astrogliosis remains unclear; however, recent observations have shown cytokines may play a pivotal role. During CNS trauma, macrophages and lymphocytes infiltrate the CNS where they are thought to synthesize and secrete cytokines; moreover, activated microglia and reactive astrocytes are known to be capable of cytokine production. We are the first to report that an intracerebral injection of the pleiotropic cytokine, ciliary neurotrophic factor (CNTF), increases astrogliosis and the appearance of activated microglia in the neonatal rat. This response to CNTF was comparable to the response observed in animals receiving a well known pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Only a moderate increase was observed in the proliferative index of cytokine-injected animals; therefore, we conclude that GFAP is largely upregulated in a pre-existing GFAP negative cell population. Interestingly, coinjections of CNTF and TNF-alpha appeared to act synergistically. Coinjected animals displayed a wave of hypertrophied astrocytes reaching far into the contralateral hemisphere. No contralateral spreading of microglia was observed. This article clearly provides interesting information regarding the regulatory mechanisms that govern astrogliosis and discusses the probable relationship of reactive astrocytes to microglia.

Animals↗
PubMed1995

Amoeboid microglia expressing GD3 ganglioside are concentrated in regions of oligodendrogenesis during development of the rat corpus callosum.

In recent study we demonstrated expression of the platelet-derived growth factor alpha receptor (PDGFR alpha) in cells of the early oligodendrocyte lineage that were identified as either GD3 ganglioside + oligodendrocyte progenitors or O4 sulfatide+ preoligodendrocytes. We also identified a subpopulation of GD3 immunoreactive cells that did not express mRNA for the PDGF receptor. The distinct large amoeboid morphology of these cells was characteristic of cells in the macrophage lineage rather than in the oligodendrocyte lineage. To determine if the GD3-positive but PDGFR alpha mRNA-negative cells were in the macrophage lineage, we compared the spatial and temporal expression patterns of GD3 ganglioside and ED1, a macrophage-specific antigen. Analysis prenatally indicated that at embryonic day 15, ED1+ and GD3+ cell populations resided in the subpial connective tissue. At embryonic day 21, these two populations were seen in a region extending from the lateral ventricle through the subventricular and intermediate zones. In this study we report that these large, round, GD3 immunoreactive cells have the same cell morphology and anatomical distribution as the ED1 immunoreactive cells. Both cell populations contained pyknotic nuclei within their cytoplasm. Furthermore, the GD3+/PDGFR alpha- cells appear to be involved in clearing cellular debris in regions of gliogenesis. These data suggest that this subpopulation of GD3 immunoreactive cells belongs to the microglia/macrophage lineage.

Animals↗
PubMed1994

Tissue-specific DNA methylation patterns of the rat glial fibrillary acidic protein gene.

The glial fibrillary acidic protein (GFAP) is an intermediate filament protein, specific of the cytoskeleton of astrocytes in the central nervous system. In the present work, as a preliminary step to the study of glial-specific gene expression, we cloned the rat GFAP gene, and we report the sequence of 1.9 kb of the 5' flanking region, exon 1, and the majority of the first intron. By digestion with methylation-sensitive restriction enzymes followed by Southern blot analysis, the methylation status of various CpG sites was examined in this genomic segment. We tested whether structural modification of the GFAP gene, such as DNA methylation, could be related to its tissue-specific transcriptional activity. Therefore, we compared a GFAP-expressing cell population (primary culture of astroglial cells), a mixed population of GFAP-expressing and -nonexpressing cells (adult rat cerebral hemispheres), and a GFAP-nonexpressing tissue (liver). In the 5' flanking region we identified a CpG site at position -1176 whose level of methylation is inversely correlated to GFAP expression. In primary cultured astrocytes, 75% of the GFAP gene alleles were demethylated at this site, while the corresponding value obtained for the cerebral hemispheres was 45%, and for liver only 9%. On the basis of the sequence data, a CpG-rich region (putative CpG island) was identified extending from -38 to +347 and overlapping 80% of the first exon. HhaI and HpaII sites located in the putative CpG island showed a relatively high level of methylation in all the cell populations examined, and did not show any clear correlation with the level of GFAP gene expression or with the methylation status of the -1176 site. Further in vivo developmental studies and in vitro differentiation studies are necessary to better understand the functional differences of the various methylatable CpG sites in the 5' end of the GFAP gene.

Animals↗
PubMed1994

Brain-specific expression of the human transferrin gene. Similar elements govern transcription in oligodendrocytes and in a neuronal cell line.

We have identified the regulatory sequences that govern the expression of the human transferrin gene in cultured brain cells and compared them with the data obtained with the neuronal cell line B103. Oligodendrocytes and epithelial choroid plexus cells from rat brain were cultured and used for transient expression experiments. Deletion analysis of 1.8 kilobase pairs of the 5' regulatory sequences revealed a -1530/-1140 positive-acting region in oligodendrocytes. The -164/+1 promoter region was sufficient to confer cell type-specific transcription in oligodendrocytes, epithelial choroid plexus cells, and B103 cells. DNase I footprinting experiments revealed three protected sequences, the proximal regions I and II, and the central region I. Gel retardation and antibody reactivity data allowed us to identify most of the nuclear factors present in oligodendrocytes interacting with the promoter sequences. Chicken ovalbumin upstream promoter transcription factor, a CAAT/enhancer-binding protein, and a cAMP response element-binding protein called CRI-BP interact with the proximal regions I and II and central region I sites, respectively. These data confirm the results obtained with the neuronal cell line and emphasize the importance of the three promoter elements for the transferrin gene-specific expression in the central nervous system compared with only two elements required for liver- and testis-specific expression.

Animals↗
PubMed1994

Platelet-derived growth factor receptor is expressed by cells in the early oligodendrocyte lineage.

We report the localization of PDGFR alpha mRNA (PDGFR alpha) in phenotypically defined cells during the first postnatal week of rat forebrain development. Using a method of combined immunocytochemistry and in situ hybridization we have demonstrated the cellular colocalization of PDGFR alpha mRNA with GD3 ganglioside or O4 sulfatide, phenotypic markers of oligodendrocytes, in the gray and white matter of the dorsal cerebral cortex at all ages studied. Population analysis of the PDGFR alpha +/GD3+ and PDGFR alpha+/O4+ cells revealed that three populations express PDGFR alpha: GD3+, GD3+/O4+, and O4+, corresponding to two lineage stages, progenitor and preoligodendrocyte, in oligodendrocyte development. Immature oligodendrocytes, identified by galactocerebroside immunoreactivity, did not express detectable levels of PDGFR alpha mRNA. Post-mitotic neurons, identified by immunoperoxidase localization of the 68 kD neurofilament, and astrocytes identified by S-100 or GFAP immunoreactivity were also negative for PDGFR alpha mRNA. The spatial and temporal expression of PDGFR alpha mRNA occurred in oligodendrocyte cell populations which are post-migratory and proliferative, but which do not express myelin proteins characteristic of post-mitotic oligodendrocytes.

Animals↗