Down-regulation of Polysialic Acid Is Required for Efficient Myelin Formation

Oligodendrocyte precursor cells modify the neural cell adhesion molecule (NCAM) by the attachment of polysialic acid (PSA). Upon further differentiation into mature myelinating oligodendrocytes, however, oligodendrocyte precursor cells down-regulate PSA synthesis. In order to address the question of whether this down-regulation is a necessary prerequisite for the myelination process, transgenic mice expressing the polysialyltransferase ST8SiaIV under the control of the proteolipid protein promoter were generated. In these mice, postnatal down-regulation of PSA in oligodendrocytes was abolished. Most NCAM-120, the characteristic NCAM isoform in oligodendrocytes, carried PSA in the transgenic mice at all stages of postnatal development. Polysialylated NCAM-120 partially co-localized with myelin basic protein and was present in purified myelin. The permanent expression of PSA-NCAM in oligodendrocytes led to a reduced myelin content in the forebrains of transgenic mice during the period of active myelination and in the adult animal. In situ hybridizations indicated a significant decrease in the number of mature oligodendrocytes in the forebrain. Thus, down-regulation of PSA during oligodendrocyte differentiation is a prerequisite for efficient myelination by mature oligodendrocytes. Furthermore, myelin of transgenic mice exhibited structural abnormalities like redundant myelin and axonal degeneration, indicating that the down-regulation of PSA is also necessary for myelin maintenance. Oligodendrocyte precursor cells modify the neural cell adhesion molecule (NCAM) by the attachment of polysialic acid (PSA). Upon further differentiation into mature myelinating oligodendrocytes, however, oligodendrocyte precursor cells down-regulate PSA synthesis. In order to address the question of whether this down-regulation is a necessary prerequisite for the myelination process, transgenic mice expressing the polysialyltransferase ST8SiaIV under the control of the proteolipid protein promoter were generated. In these mice, postnatal down-regulation of PSA in oligodendrocytes was abolished. Most NCAM-120, the characteristic NCAM isoform in oligodendrocytes, carried PSA in the transgenic mice at all stages of postnatal development. Polysialylated NCAM-120 partially co-localized with myelin basic protein and was present in purified myelin. The permanent expression of PSA-NCAM in oligodendrocytes led to a reduced myelin content in the forebrains of transgenic mice during the period of active myelination and in the adult animal. In situ hybridizations indicated a significant decrease in the number of mature oligodendrocytes in the forebrain. Thus, down-regulation of PSA during oligodendrocyte differentiation is a prerequisite for efficient myelination by mature oligodendrocytes. Furthermore, myelin of transgenic mice exhibited structural abnormalities like redundant myelin and axonal degeneration, indicating that the down-regulation of PSA is also necessary for myelin maintenance. Polysialic acid (PSA), 3The abbreviations used are: PSA, polysialic acid; MAG, myelin-associated glycoprotein; MBP, myelin basic protein; NCAM, neural cell adhesion molecule; OPC, oligodendrocyte precursor cell(s); PDGF, platelet-derived growth factor; PLP, proteolipid protein; PBS, phosphate-buffered saline; HPTLC, high performance TLC; endoN, endoneuraminidase; TUNEL, terminal dUTP nick-end labeling; Pn, postnatal day n; GM1, Galβ3GalNAcβ4-(Neu5Acα3)Galβ4Glc-ceramide; GD1a, Neu5Acα3Galβ3GalNAcβ4(Neu5-Acα3)Galβ4Glc-ceramide; GD1b, Galβ3GalNAcβ4(Neu5Acα8Neu5Acα3)-Galβ4Glc-ceramide; GT1b, Neu5Acα3Galβ3GalNAcβ4(Neu5Acα8Neu5-Acα3)Galβ4Glc-ceramide.3The abbreviations used are: PSA, polysialic acid; MAG, myelin-associated glycoprotein; MBP, myelin basic protein; NCAM, neural cell adhesion molecule; OPC, oligodendrocyte precursor cell(s); PDGF, platelet-derived growth factor; PLP, proteolipid protein; PBS, phosphate-buffered saline; HPTLC, high performance TLC; endoN, endoneuraminidase; TUNEL, terminal dUTP nick-end labeling; Pn, postnatal day n; GM1, Galβ3GalNAcβ4-(Neu5Acα3)Galβ4Glc-ceramide; GD1a, Neu5Acα3Galβ3GalNAcβ4(Neu5-Acα3)Galβ4Glc-ceramide; GD1b, Galβ3GalNAcβ4(Neu5Acα8Neu5Acα3)-Galβ4Glc-ceramide; GT1b, Neu5Acα3Galβ3GalNAcβ4(Neu5Acα8Neu5-Acα3)Galβ4Glc-ceramide. a linear homopolymer of N-acetyl-neuraminic acid, is a posttranslational modification of the neural cell adhesion molecule (NCAM) (1.Angata K. Fukuda M. Biochimie (Paris). 2003; 85: 195-206Crossref PubMed Scopus (187) Google Scholar). NCAM occurs in various isoforms that are generated by alternative splicing (2.Eckhardt M. Mühlenhoff M. Bethe A. Koopman J. Frosch M. Gerardy-Schahn R. Nature. 1995; 373: 715-718Crossref PubMed Scopus (266) Google Scholar). The three major isoforms of NCAM are the two transmembrane proteins NCAM-180 and NCAM-140 and the glycosylphosphatidylinositol-linked NCAM-120. The latter is the predominant isoform in oligodendrocytes (3.Goridis C. Brunet J.F. Semin. Cell Biol. 1992; 3: 189-197Crossref PubMed Scopus (143) Google Scholar). PSA is synthesized in the Golgi apparatus by two sialyltransferases, ST8SiaIV (4.Bhat S. Silberberg D.H. J. Neurochem. 1988; 50: 1830-1838Crossref PubMed Scopus (48) Google Scholar, 5.Nakayama J. Fukuda M.N. Fredette B. Ranscht B. Fukuda M. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 7031-7035Crossref PubMed Scopus (218) Google Scholar) and ST8SiaII (6.Kojima N. Yoshida Y. Kurosawa N. Lee Y.C. Tsuji S. FEBS Lett. 1995; 360: 1-4Crossref PubMed Scopus (104) Google Scholar, 7.Livingston B.D. Paulson J.C. J. Biol. Chem. 1993; 268: 11504-11507Abstract Full Text PDF PubMed Google Scholar). Although in the mammalian brain, polysialylated NCAM (PSA-NCAM) is mainly found in neurons, other cell types within the central nervous system synthesize PSA-NCAM as well. Migrating oligodendrocyte precursor cells (OPC) express PSA, which is, however, down-regulated after these cells reach their final destination and start to differentiate into mature myelinating oligodendrocytes (8.Trotter J. Bitter-Suermann D. Schachner M. J. Neurosci. Res. 1989; 22: 369-383Crossref PubMed Scopus (140) Google Scholar, 9.Bartsch U. Kirchhoff F. Schachner M. J. Neurocytol. 1990; 19: 550-565Crossref PubMed Scopus (85) Google Scholar, 10.Nait-Oumesmar B. Vignais L. Duhamel-Clerin E. Avellana-Adalid V. Rougon G. Baron-van Evercooren A. Eur. J. Neurosci. 1995; 7: 480-491Crossref PubMed Scopus (133) Google Scholar). The presence of PSA seems to be functionally important, since migration of OPC is impaired after endoneuraminidase treatment, which specifically hydrolyzes PSA (11.Wang C. Pralong W.F. Schulz M.F. Rougon G. Aubry J.M. Pagliusi S. Robert A. Kiss J.Z. J. Cell Biol. 1996; 135: 1565-1581Crossref PubMed Scopus (155) Google Scholar). More recent data suggest that PSA is not required for cellular motility in general but for directional movement of OPC in response to platelet-derived growth factor (PDGF) (12.Zhang H. Vutskits L. Calaora V. Durbec P. Kiss J.Z. J. Cell Sci. 2004; 117: 93-103Crossref PubMed Scopus (101) Google Scholar). In addition to its effect on migration, PSA seems also to inhibit differentiation of OPC into mature myelinating oligodendrocytes, because removal of PSA by endoneuraminidases accelerates oligodendrocyte differentiation (13.Decker L. Durbec P. Rougon G. Evercooren A.B. Mol. Cell. Neurosci. 2002; 19: 225-238Crossref PubMed Scopus (41) Google Scholar). PSA is also down-regulated in neurons at the time when their axons become myelinated. Axons that remain nonmyelinated in the adult (e.g. mossy fibers in the hippocampus) in contrast remain PSA-positive (14.Seki T. Arai Y. Neurosci. Res. 1991; 12: 503-513Crossref PubMed Scopus (183) Google Scholar, 15.Le Gal La Salle G. Rougon G. Valin A. J. Neurosci. 1992; 12: 872-882Crossref PubMed Google Scholar). These observations together with the fact that premature removal of PSA accelerates myelin formation led to the hypothesis that PSA expressed on the axonal membrane is an inhibitor of myelination (16.Charles P. Hernandez M.P. Stankoff B. Aigrot M.S. Colin C. Rougon G. Zalc B. Lubetzki C. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 7585-7590Crossref PubMed Scopus (243) Google Scholar). This is supported by the observation that premature removal of PSA by endoneuraminidase increases myelin formation in vivo and in vitro (16.Charles P. Hernandez M.P. Stankoff B. Aigrot M.S. Colin C. Rougon G. Zalc B. Lubetzki C. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 7585-7590Crossref PubMed Scopus (243) Google Scholar). The re-expression of PSA in multiple sclerosis lesions (17.Charles P. Reynolds R. Seilhean D. Rougon G. Aigrot M.S. Niezgoda A. Zalc B. Lubetzki C. Brain. 2002; 125: 1972-1979Crossref PubMed Scopus (227) Google Scholar) and hypomyelinated mice (18.Takikita S. Fukuda T. Mohri I. Yagi T. Suzuki K. J. Neuropathol. Exp. Neurol. 2004; 63: 660-673Crossref PubMed Scopus (63) Google Scholar) might therefore be one factor inhibiting (re)myelination. Accelerated oligodendrocyte differentiation and myelin formation by premature removal of PSA suggests but does not prove that the normal postnatal down-regulation of PSA is a prerequisite for myelination. In order to further address this question and to discriminate between PSA-dependent effects in oligodendrocytes and neurons, we have generated transgenic mice overexpressing the polysialyltransferase ST8SiaIV in neurons and oligodendrocytes. In the present study, we asked whether down-regulation of PSA in OPC is a secondary effect of the differentiation process or whether PSA down-regulation is a prerequisite for myelin formation. Using transgenic mice overexpressing the polysialyltransferase ST8SiaIV in oligodendrocytes via the proteolipid protein (PLP) promoter, we show here that the continuous expression of PSA in mature oligodendrocytes causes hypomyelination. Generation of PLP-PST Transgenic Mice−Mouse ST8SiaIV was amplified by PCR using oligonucleotides PSTsense and with and are in the with and into the of the promoter B. Mol. Cell. Neurosci. PubMed Scopus Google Scholar) by B. of ST8SiaIV was by In order to transgenic mice, were the by the with and by The was and purified using and into mice was at the for mice were by using a ST8SiaIV as H. N. V. M. J. Neurochem. PubMed Scopus Google Scholar). mice were which two transgenic and were and on a of mice was by PCR on using oligonucleotides PSTsense and as which in a in the presence of the Oligodendrocyte and were the forebrains of mice day or J. J. Cell Biol. 85: PubMed Scopus Google Scholar, J. P. Schachner M. Exp. Neurol. 1990; PubMed Scopus Google Scholar). were and in with in with for Cell were as and in with when cells oligodendrocyte precursor cells on of the were and on at a of and in with with were in in were for in in PBS, and cells were with were with myelin basic protein in in In cells were with PSA M. I. Bitter-Suermann D. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google by A. M. of and NCAM PSA were with NCAM were with and in were with were in and with an In was to using the was using as by the was in and were generated with by using the the of the was as J. T. Scholar). were to by to In for and were synthesized as H. N. V. M. J. Neurochem. PubMed Scopus Google Scholar, A. V. M. Eur. J. Neurosci. PubMed Scopus Google Scholar). ST8SiaIV was into the and for were a in was amplified by using oligonucleotides and The PCR was into the of and were with or and the of the In situ on or was as H. N. V. M. J. Neurochem. PubMed Scopus Google Scholar). were with and as were with a of were in and at or were at at and in in for were with at were with and were with in for at PSA and were with and in were with and in were with were in and with a to an were with the of cells were using with terminal using a to the were in in PBS, with for and with and terminal in for at was using and as were or purified myelin and as A. V. M. Eur. J. Neurosci. PubMed Scopus Google Scholar). were by were in and and were as were by using In myelin were in were by with in acid by a at was the of and transgenic mice at various time as by and J. Neurochem. PubMed Scopus Google Scholar). were in using an were for with The of the was in with and for with was the with and to a in order to myelin was with in and in at In order to the of myelin in the brain, the purified myelin was and the was protein and myelin were in were using the protein In were in all and and were in were by of the at for by of the at for or was using E. D. Scholar). was with as the using the as E. D. Scholar). The were R. and were with in and were in the were using the secondary by with as M. I. V. J. 2002; PubMed Google Scholar). In were with endoneuraminidase R. for at were with in by and of linear were by using were for significant using and with and was as H. J. Neurocytol. 7: PubMed Scopus Google Scholar). Generation of PLP-PST Transgenic mice expressing the polysialyltransferase ST8SiaIV under the control of the promoter were generated transgenic mice were by and two transgenic and were and on a of the was by using a These a significant in the expression between postnatal day and adult mice In the was In situ hybridizations of with a ST8SiaIV indicated expression of the in oligodendrocytes in the of and as of the ST8SiaIV expression required and is therefore not here not and of the not to be in the transgenic mice, and we not in the postnatal of the which is reduced in in mice H. R. A. M. G. J. R. S. P. S. D. K. Nature. PubMed Scopus Google Scholar, H. K. D. C. C. U. T. 1993; Full Text PDF PubMed Scopus Google Scholar). of that PSA was in the adult of transgenic mice was also in mice in with observations J. Bitter-Suermann D. C. U. J. Google Scholar, M. G. L. C. Schachner M. Gerardy-Schahn R. H. A. J. Neurosci. 2000; PubMed Google Scholar). the with that the NCAM-120 were reduced in the transgenic because of the to the presence of of with endoneuraminidase to PSA indicated that the of all NCAM isoforms was not in the transgenic mice and that NCAM-120 is the major NCAM isoform in in the of transgenic mice was The presence of PSA in oligodendrocytes was further by on and of adult using and PSA in the of mice was to the the PSA-positive neural are generated in the adult F. A. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google but was (e.g. the In PSA was expressed in the and other in the and of transgenic PSA partially co-localized with indicating the presence of PSA-NCAM in myelin. of PSA and in was are the however, were with transgenic mice of the of PSA in of PLP-PST Transgenic order to address the question of whether the presence of PSA with protein were in the of adult and transgenic mice that with mice, were reduced in transgenic of of transgenic and mice at indicated that the down-regulation of protein was in to reduced expression were in transgenic mice to of but normal in In expression of the oligodendrocyte which to be expressed during oligodendrocyte was in and transgenic mice at all time and In order to reduced myelin content in transgenic mice, myelin was purified the forebrains of transgenic and mice at time and of and its was found a significant in the myelin content at and The of the at was not because of the myelin content at this in the myelin was These the presence of polysialylated NCAM-120 in myelin The of NCAM-120 in myelin however, not reduced in the myelin of transgenic mice of other myelin MBP, not in the of these proteins in purified myelin Furthermore, of not in the myelin protein between transgenic and mice not In order to the that of ST8SiaIV other because of the of acid for and purified myelin were by using the acid significant in the were and Furthermore, we the and purified myelin of adult transgenic and were by In the we found a significant in the in the transgenic In the of two other and were In purified however, the of and was not in transgenic mice as with therefore that the of ST8SiaIV not inhibit of but that the reduced in the and in of in Transgenic myelin content and expression be to in the time of oligodendrocyte the number of mature oligodendrocytes, or formation of the myelin is expressed in mature oligodendrocytes, we that differentiation of oligodendrocytes not be in the transgenic In order to prove this we the number of mature oligodendrocytes in the at time and of by in situ of of PLP-PST transgenic mice and using the number of cells in the was reduced in transgenic mice at and of of in the number of cells was and was significant in the transgenic hybridizations were with a of the as a for OPC we not a decrease in cell number in the transgenic at and of This that the number of OPC was not reduced in the transgenic mice, which was since the ST8SiaIV not be expressed at the of reduced of cells be to cell was in order to cells were in the forebrains of and transgenic mice at and an in the number of cells in the transgenic not be In order to we the in situ hybridizations with for mature oligodendrocytes, transgenic mice and were to The number of cells in the was reduced in transgenic mice The observation of a reduced number of cells in transgenic mice was because the ST8SiaIV be expressed in mature oligodendrocytes. is that the of ST8SiaIV expression further differentiation to mature oligodendrocytes and further of expression that the the of the in situ In of Transgenic asked whether presence of PSA of oligodendrocytes in were mice and for OPC on of the OPC were in and the number of cells a for mature was between and of differentiation The of cells in transgenic was not Thus, in vitro differentiation of oligodendrocytes was not or in the presence of in mature oligodendrocytes mice were In oligodendrocytes transgenic mice were PSA-positive PSA was the cell but was also found in the of oligodendrocytes. Transgenic oligodendrocytes a mature with and membrane for PSA and NCAM of PSA and NCAM in the membrane of oligodendrocytes in the which PSA the NCAM was and PSA and NCAM not that other proteins NCAM carried PSA in the transgenic oligodendrocytes ST8SiaIV is and is that the PSA is to however, the that other were by the The of NCAM and in the membrane were not in the transgenic cells as with and expression in oligodendrocytes. purified oligodendrocytes and transgenic mice were for in and for PSA and NCAM of of the transgenic cell in significant of PSA and NCAM in the cell but not in the in are in oligodendrocytes for were with an were with in and and of in myelin content was were in mice to an of however, we and in a of transgenic mice of the The for this might be the the central nervous system of adult transgenic mice by for myelin abnormalities like redundant myelination axonal and in the and the not were in transgenic but not in These abnormalities were in all transgenic however, mice of the a Furthermore, we found for in the transgenic in these mice was also in the not a was in one we the of a The presence of in however, with the expression in this Furthermore, this also a effect of the expression on oligodendrocyte differentiation and myelin formation Thus, the of the in the might be by the expression Oligodendrocyte differentiation and myelination of axons in the central nervous system are by and I. G. P. Zalc B. Lubetzki C. J. Neurol. Sci. Full Text Full Text PDF PubMed Scopus Google Scholar). are to the premature differentiation of OPC and myelination reach their final for of myelination are the R. S. S. J. Neurosci. 19: PubMed Google Scholar) and S. Lee S. J. G. M. M. C. D. B. V. J.M. Neurosci. PubMed Scopus Google Scholar). of myelination is PSA is required for the migration of OPC as using or OPC mice (11.Wang C. Pralong W.F. Schulz M.F. Rougon G. Aubry J.M. Pagliusi S. Robert A. Kiss J.Z. J. Cell Biol. 1996; 135: 1565-1581Crossref PubMed Scopus (155) Google Scholar). More recent observations that PSA is also required for the migration of OPC (12.Zhang H. Vutskits L. Calaora V. Durbec P. Kiss J.Z. J. Cell Sci. 2004; 117: 93-103Crossref PubMed Scopus (101) Google Scholar). Upon differentiation of OPC into oligodendrocyte and mature oligodendrocytes, PSA is down-regulated (8.Trotter J. Bitter-Suermann D. Schachner M. J. Neurosci. Res. 1989; 22: 369-383Crossref PubMed Scopus (140) Google Scholar, 9.Bartsch U. Kirchhoff F. Schachner M. J. Neurocytol. 1990; 19: 550-565Crossref PubMed Scopus (85) Google Scholar). is mainly by reduced ST8SiaIV J. Neurosci. Res. PubMed Scopus Google Scholar). oligodendrocytes to the of the promoter in the transgenic down-regulation of PSA was in transgenic mice and NCAM-120, the predominant glycosylphosphatidylinositol-linked NCAM isoform in oligodendrocytes, was synthesized as polysialylated Although NCAM is the major other proteins be polysialylated (e.g. the M. M. Bethe A. Frosch M. Gerardy-Schahn R. J. 1996; PubMed Scopus Google Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In the oligodendrocyte we PSA in the of these proteins are the ST8SiaIV other proteins is of however, not to a general in the of other or The ST8SiaIV also not the of NCAM or in the oligodendrocyte Furthermore, the of purified myelin was not in the transgenic These observations suggest that the expression not of myelin membrane however, the that attachment of PSA to proteins that were in oligodendrocytes is in for the This be by overexpressing ST8SiaIV in PSA down-regulation was the number of oligodendrocytes in the was This observation was because one that cells express the which is under the control of the of this observation is that a of the promoter of the is to the number of the to in the of PSA-NCAM that further differentiation and further of The of the promoter might in expression that are the of the in situ I. S. F. P. Fukuda M. Rougon G. Durbec P. M. Mol. Cell. Neurosci. 2004; PubMed Scopus Google Scholar) that neural precursor cells into the of mice myelination. myelination this was by down-regulation of PSA I. S. F. P. Fukuda M. Rougon G. Durbec P. M. Mol. Cell. Neurosci. 2004; PubMed Scopus Google Scholar). PSA down-regulation at the PSA down-regulation was in vivo in I. S. F. P. Fukuda M. Rougon G. Durbec P. M. Mol. Cell. Neurosci. 2004; PubMed Scopus Google Scholar) that the axons might the down-regulation of PSA synthesis. In contrast to this study, we not down-regulation of PSA during myelination in The for these observations is not but might be to the expression used protein show that myelin formation does not of PSA the oligodendrocyte since myelin was in the transgenic mice, and PSA-NCAM partially co-localized with and was present in purified myelin. however, and myelin to be Furthermore, PSA of myelin and of oligodendrocytes, as indicated by redundant myelination and axonal The in mice of one transgenic the that the presence of of PSA in myelin with myelin at we the of a mice have generated by ST8SiaIV and ST8SiaII B. R. I. Mühlenhoff M. F. S. Gerardy-Schahn R. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In these mice, the of was was not whether this myelination or reduced The of the and other in mice to be secondary to the B. R. I. Mühlenhoff M. F. S. Gerardy-Schahn R. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the of these mice be by NCAM, seems that an of PSA is to NCAM during B. R. I. Mühlenhoff M. F. S. Gerardy-Schahn R. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the effect of PSA on the number of mature oligodendrocytes and myelin formation be to NCAM mice mice in this in myelin formation of the central nervous system of mice, however, have not and myelination was normal in S. D. H. Schachner M. R. Cell Res. PubMed Scopus Google Scholar). Furthermore, at in the the number of oligodendrocytes was found to be G. Durbec P. A. Rougon G. H. J. Neurosci. 2000; PubMed Google Scholar). these data suggest that of myelin formation and myelin in mice is not to a of NCAM by the presence of PSA inhibit myelin of PSA with not NCAM but also adhesion between other cell like or A. U. J. Cell Biol. 1991; PubMed Scopus Google Scholar, I. U. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). to the U. J. 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J. Neurosci. PubMed Google Scholar). R. A. F. Gerardy-Schahn R. H. Mol. Cell. Biol. 2003; PubMed Scopus Google Scholar) that of cells the protein Thus, the PSA modification of NCAM a effect on in oligodendrocytes a mature with and membrane observations have by I. S. F. P. Fukuda M. Rougon G. Durbec P. M. Mol. Cell. Neurosci. 2004; PubMed Scopus Google Scholar). therefore that the presence of PSA on NCAM-120 in oligodendrocytes with required for efficient process and of myelin that might be by is which is for oligodendrocyte differentiation C. B. R. J. J. Neurosci. 2002; 22: PubMed Google Scholar, J. Neurosci. 2004; PubMed Scopus Google Scholar) and of expression H. Y. K. Yoshida Y. K. H. T. J. Neurosci. 19: PubMed Google Scholar) and which with NCAM-120 in C. T. M. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In we not in the in purified myelin in transgenic is that an of via or is during the of myelination. In addition to its effect on oligodendrocyte differentiation (13.Decker L. Durbec P. Rougon G. Evercooren A.B. Mol. Cell. Neurosci. 2002; 19: 225-238Crossref PubMed Scopus (41) Google Scholar) and myelin the continuous of PSA-NCAM also myelin in the adult animal. abnormalities of myelin and were These observations show that PSA down-regulation is not necessary for efficient differentiation of oligodendrocytes and myelin formation but that its presence in myelin also with the of the myelin and axonal by oligodendrocytes. I. and M. for B. for the promoter P. for with the oligodendrocyte A. for and R. Gerardy-Schahn for and