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Oligodendrocyte Development (oligodendrocyte + development)
Selected AbstractsSymposium 8: Regulation of Oligodendrocyte DevelopmentJOURNAL OF NEUROCHEMISTRY, Issue 2002R. H. Miller Oligodendrocyte precursors arise in restricted regions of the developing neuroepithelium due to local signals that include sonic hedgehog. In the spinal cord the founder cells of the oligodendrocyte lineage develop in a specific domain of the ventral ventricular zone. These cells or their progeny subsequently migrate long distances to populate the entire spinal cord and myelinate axons in the peripheral presumptive white matter. The majority of migration in the oligodendrocyte lineage is accomplished by immature precursors, which then stop, proliferate and differentiate in the appropriate location. Several distinct mechanisms appear to regulate this migration. The initial dispersal of cells from the ventral ventricular zone is guided by chemorepellent cues including netrin-1 present in the ventral ventricular domain. Migratory precursors are arrested in particular locations within the developing spinal cord as the result of the localized expression of the chemokine, CXCL1 by astrocytes. This chemokine, signalling through the CXCR2 receptor combines with PDGF to inhibit cell migration and enhance cell proliferation thereby facilitating the local expansion of the oligodendrocyte lineage and myelination of all relevant axons. [source] Control of oligodendrocyte generation and proliferation by Shp2 protein tyrosine phosphataseGLIA, Issue 12 2010Ying Zhu Abstract Extracellular signals play essential roles in controlling the proliferation and differentiation of oligodendrocyte progenitor cells in the developing central nervous system. However, the intracellular pathways that transduce these extrinsic signals remain to be elucidated. In this study, we showed that conditional ablation of the nonreceptor tyrosine phosphatase Shp2 in Olig1-expressing oligodendrocyte lineage resulted in dramatic reduction in the generation and proliferation of oligodendrocyte progenitor cells in the spinal cord. Maturation and myelination of oligodendrocytes were also compromised in the Shp2 mutants. The deficits in oligodendrocyte development in Shp2 mutants nearly phenocopied those observed in PDGF-A mutants, suggesting that Shp2 is a crucial component in transducing PDGF-A signals in the control of oligodendrocyte proliferation and maturation. © 2010 Wiley-Liss, Inc. [source] Early stages of oligodendrocyte development in the embryonic murine spinal cord proceed normally in the absence of Hoxa2GLIA, Issue 1 2004Danette J. Nicolay Abstract Recent discoveries have enhanced our knowledge of the transcriptional control of oligodendrocyte (OG) development. In particular, the transcription factors (TFs) Olig2, Pax6, and Nkx2.2 have been shown to be important in the specification and/or maturation of the OG lineage. Although numerous other TFs are expressed by OGs, little is known regarding their role(s) in oligodendrogenesis. One such TF is the homeobox gene Hoxa2, which was recently shown to be expressed by O4+ pro-oligodendrocytes. The objectives of this study were to examine the expression of Hoxa2 during the early stages of OG development, as well as to determine whether Hoxa2 is required for specification and/or early maturation of OGs. Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxa2 was expressed throughout oligodendrogenesis, diminishing only with the acquisition of a myelinating phenotype. Serial transverse spinal cord sections from embryonic days 12.5, 14.25, 16, and 18 Hoxa2+/+, Hoxa2+/,, and Hoxa2,/, mice were subjected to single and double immunohistochemical analysis in order to examine Hoxa2, Olig2, Nkx2.2, and Pax6 expression profiles. Results obtained from Hoxa2+/+ and Hoxa2+/, mice suggested that Hoxa2 was expressed by migratory oligodendroglial cells. In addition, comparison of spinal cord sections obtained from Hoxa2+/+, Hoxa2+/,, and Hoxa2,/, mice suggested that specification and early maturation of OGs proceeded normally in the absence of Hoxa2, since there were no obvious alterations in the expression patterns of Olig2, Nkx2.2, and/or Pax6. Hence, although Hoxa2 is expressed throughout OG development, it does not appear to be critical for early stages of oligodendrogenesis in the murine spinal cord. © 2004 Wiley-Liss, Inc. [source] Modulation of peroxisome proliferator-activated receptor-, activity by N -acetyl cysteine attenuates inhibition of oligodendrocyte development in lipopolysaccharide stimulated mixed glial culturesJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Manjeet K. Paintlia Abstract Glial cells secrete proinflammatory mediators in the brain in response to exogenous stimuli such as infection and injury. Previously, we documented that systemic maternal lipopolysaccharide (LPS)-exposure at embryonic gestation day 18 causes oligodendrocyte (OL)-injury/hypomyelination in the developing brain which can be attenuated by N -acetyl cysteine (NAC; precursor of glutathione). The present study delineates the underlying mechanism of NAC-mediated attenuation of inhibition of OL development in LPS-stimulated mixed glial cultures. Factors released by LPS-stimulated mixed glial cultures inhibited OL development as shown by decrease in both proliferation 3bromo-deoxyuridine+/chondroitin sulfate proteoglycan,NG2+, hereafter BrdU+/NG+ and differentiation (O4+ and myelin basic protein+) of OL-progenitors. Correspondingly, an impairment of peroxisomal proliferation was shown by a decrease in the level of peroxisomal proteins in the developing OLs following exposure to LPS-conditioned media (LCM). Both NAC and WY14643, a peroxisome proliferator-activated receptor (PPAR)-, agonist attenuated these LCM-induced effects in OL-progenitors. Similar to WY14643, NAC attenuated LCM-induced inhibition of PPAR-, activity in developing OLs. Studies conducted with cytokines and diamide (a thiol-depleting agent) confirmed that cytokines are active agents in LCM which may be responsible for inhibition of OL development via peroxisomal dysfunction and induction of oxidative stress. These findings were further corroborated by similar treatment of developing OLs generated from PPAR-,(,/,) and wild-type mice or B12 oligodendroglial cells co-transfected with PPAR-, small interfering RNAs/pTK-PPREx3-Luc plasmids. Collectively, these data provide evidence that the modulation of PPAR-, activity, thus peroxisomal function by NAC attenuates LPS-induced glial factors-mediated inhibition of OL development suggesting new therapeutic interventions to prevent the devastating effects of maternal infections. [source] Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2008Jahan Ara Abstract Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up-regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG-peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT-PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2- to 4-fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle-treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG-peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up-regulated during EAE. © 2007 Wiley-Liss, Inc. [source] | ||||||||||