Abstract Three monoclonal antibodies that react with antigens on the surface of developing oligodendrocytes in a stage‐specific manner, 01, 04 (Sommer and Schachner, 1981), R‐mAb (Ranscht et al., 1982), have been studied respect to their specificities for number purified lipids. The observed were consistent regardless how presented antibodies. 01 reacted galactocerebroside, monogalactosyl‐diglyceride, psychosine and, addition, labeled an unidentified species rat brain extracts. sulfatide,...

Wrapping of the myelin sheath around axons by oligodendrocytes is critical for rapid conduction electrical signals required normal functioning CNS. Myelination a multistep process where progress through well coordinated differentiation program regulated multiple extracellular growth and signals. The intracellular transduction that regulate myelination poorly understood. Here we demonstrate role two important signaling molecules, extracelluar signal-regulated protein kinases 1 2 (ERK1/ERK2),...

Myelin is a biologically active membrane receiving and processing signals from axons. Although much known about its structure molecular composition, the intracellular signal transduction pathways, during specific phases of myelinogenesis for regulating myelin formation, remain poorly understood. Recent genetic loss-of-function studies have suggested key role extracelluar signal-regulated kinases-1 -2 (ERK1/2), downstream mediators mitogen-activated protein kinases (MAPKs), in promoting CNS...

Abstract: Evidence is presented for the immunological identification of a developmental antigen appearing at critical point in oligodendroglial lineage. Specifically, monoclonal antibody A007 recognizes cells oligodendrocyte lineage two distinct stages. Analyses purified lipid standards and extracts from galactocerebroside‐positive (GalC + ) oligodendrocytes by enzyme‐linked immunosorbent assay, dot blot, immuno‐TLC demonstrated that sulfatide (SUL) seminolipid. However, neither 35 SO 4...

Abstract Myelination is the culmination of a complex process in which oligodendrocyte (OL) progenitors transition through defined stages well‐coordinated differentiation program. The signaling mechanisms that regulate this progression are poorly understood. Here we investigate role extracellular signal‐regulated‐kinase‐1,‐2 (Erk1/2) and mammalian target rapamycin (mTOR), downstream effectors Ras/Raf/Mek/Erk PI3K/Akt/mTOR pathways, at specific OL development vitro . Using panel developmental...

We have previously shown that myelin abnormalities characterize the normal aging process of brain and an age-associated reduction in Klotho is conserved across species. Predominantly generated kidney, overexpression extends life span, whereas loss accelerates development aging-like phenotypes. Although function unknown, expression leads to cognitive deficits. found significant effects on oligodendrocyte functions, including induced maturation rat primary oligodendrocytic progenitor cells...

Formation of the CNS white matter is developmentally tightly regulated, but molecules and mechanisms myelination control in postnatal are poorly understood. Here, we show that myelin growth controlled by fibroblast factor (FGF) signaling, originally identified as a proliferative signal for oligodendrocyte precursor cells (OPCs) vitro . We created two lines mice lacking both FGF receptor 1 (Fgfr1) Fgfr2 oligodendrocyte-lineage found these OPC proliferation differentiation were unaffected. In...

Multiple extracellular and intracellular signals regulate the functions of oligodendrocytes as they progress through complex process developmental myelination then maintain a functionally intact myelin sheath throughout adult life, preserving integrity axons. Recent studies suggest that Mek/ERK1/2-MAPK PI3K/Akt/mTOR signaling pathways play important, often overlapping roles in regulation myelination. However, it remains poorly understood whether function independently, sequentially, or...

ABSTRACT Oligodendrocytes, the myelinating cells of vertebrate CNS, originally develop from neuroepithelium. Recent studies suggest that spinal cord oligodendrocyte precursors are initially localized in region ventral ventricular zone and subsequently disperse throughout cord. The characteristics these early their subsequent migration has been difficult to assay directly rodent due a lack appropriate reagents. In developing chick cord, we show can be specifically identified by labeling with...

Fibroblast growth factors (FGFs) have been implicated in numerous cellular processes, including proliferation, migration, differentiation, and survival. Whereas FGF-2, the prototypic ligand a family of 22 members, activates all four tyrosine kinase FGF receptors (FGFR1-FGFR4), other members demonstrate higher degree selectivity. Oligodendrocytes (OLs), myelin-producing cells CNS, are highly influenced by FGF-2 at stages their development. However, how FGFs cognate orchestrate development OLs...

Axoglial interactions underlie the clustering of ion channels and cell adhesion molecules, regulate gene expression, control survival. We report that Cnp1-null mice, lacking expression myelin protein cyclic nucleotide phosphodiesterase (CNP), have disrupted axoglial in central nervous system (CNS). Nodal sodium (Nav) paranodal proteins (Caspr) are initially clustered normally, but become progressively disorganized with age. These changes characterized by mislocalized Caspr immunostaining,...

Paranodal axoglial junctions in myelinated nerve fibers are essential for efficient action potential conduction and ion channel clustering. We show here that, the mature CNS, a fraction of oligodendroglial 155 kDa isoform neurofascin (NF-155), major constituent paranodal junctions, has key biochemical characteristics lipid raft-associated protein. However, despite its robust expression, NF-155 is detergent soluble before paranodes form purified oligodendrocyte cell cultures. Only during...

We have hypothesized that oligodendrocyte (OL) surface glycolipids, specifically galactocerebroside and sulfatide, play a role in the regulation of OL development by acting as sensors/transmitters environment information. In support this hypothesis we report here reversible inhibition progenitor cell differentiation monoclonal antibody [Ranscht mAb (R-mAb); Ranscht, B., Clapshaw, P. A. & Seifert, W. (1982) Proc. Natl. Acad. Sci. USA 79, 2709-2713] reacts with these glycolipids. When...

Myelin, formed by oligodendrocytes (OLs) in the CNS, is critical for axonal functions, and its damage leads to debilitating neurological disorders such as multiple sclerosis. Understanding molecular mechanisms of myelination pathogenesis human myelin disease has been limited partly relative lack identification functional characterization repertoire proteins. Here, we present a large-scale analysis proteome, using shotgun approach 1-dimensional PAGE liquid chromatography/tandem MS. Three...

Fibroblast growth factors (FGFs) comprise a family of developmental regulators implicated in wide variety neurological functions. FGF receptors 1, 2, and 3 ( Fgfrs ) are expressed the embryonic forebrain, including regions overlapping with ventral sites oligodendrocyte progenitor (OLP) generation. Although signaling is known to influence proliferation OLPs vitro , functions different vivo lacking. Here, we examined single double mutants conditional disruption specifically investigate effect...

Oligodendrocytes form myelin during postnatal development and then maintain a functional sheath throughout adult life. While many regulators of developmental myelination have been identified, the signal transduction mechanisms that regulate oligodendrocyte functions in adulthood are not well understood. The extracellular signal-regulated kinases-1 -2 (ERK1/2), downstream mediators mitogen-activated protein kinases (MAPKs), emerged as prominent formation. Here, we investigated whether these...

Myelin growth is a tightly regulated process driven by multiple signals. ERK1/2-MAPK signaling an important regulator of myelin thickness. Because, in demyelinating diseases, the formed during remyelination fails to achieve normal thickness, increasing ERK1/2 activity oligodendrocytes obvious therapeutic potential for promoting efficient remyelination. However, other studies have suggested that increased levels could, fact, detrimental effects on myelinating cells. Because strength,...

Galactocerebroside and sulfatide, major galactosphingolipid components of oligodendrocyte plasma membranes myelin, are first expressed at a critical point, when progenitors cease to proliferate commence terminal differentiation. We showed previously that an antibody galactocerebroside/sulfatide arrested differentiation, suggesting role for these galactolipids in have now investigated the differentiation oligodendrocytes (1) response other anti-galactolipid antibodies, showing anti-sulfatide...

Abstract The developmentally regulated appearance of surface immuno‐reactivity proligodendroblasts [oligodendrocyte progenitors reacting with monoclonal antibodies A007 and O4, but not anti‐galactocerebroside (GalC), i.e., A007/O4 + GalC − ] to R‐mAb O1 was studied both in culture vivo. In cases staining shortly preceded that O1; is, a transient population cells observed. were detected. Differential also noted at the subcellular level. younger cultures which first acquiring immunoreactivity,...

Intraventricular hemorrhage (IVH) results in neural cell death and white matter injury premature infants. No therapeutic strategy is currently available against this disorder. Bone morphogenetic protein (BMP) signaling suppresses oligodendrocyte development through basic-helix-loop-helix (bHLH) transcription factors promotes astrocytosis. Therefore, we hypothesized that IVH newborns initiates degeneration maturation arrest of lineage BMP inhibition alleviates hypomyelination, gliosis, motor...