Linked Life Data

10479693

Source:http://linkedlifedata.com/resource/pubmed/id/10479693

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1999-10-4
pubmed:abstractText
Galactocerebroside and sulfatide, major galactosphingolipid components of oligodendrocyte plasma membranes and myelin, are first expressed at a critical point, when progenitors cease to proliferate and commence terminal differentiation. We showed previously that an antibody to galactocerebroside/sulfatide arrested terminal differentiation, suggesting a role for these galactolipids in oligodendrocyte differentiation. We have now investigated the differentiation of oligodendrocytes (1) in response to other anti-galactolipid antibodies, showing that anti-sulfatide O4 but not anti-galactocerebroside O1 blocks terminal differentiation, perhaps by mimicking an endogenous ligand, and (2) in a transgenic mouse unable to synthesize these lipids because of mutation of the gene for ceramide galactosyltransferase, a key enzyme for galactosphingolipid synthesis. We find that galactosyltransferase mRNA expression begins at the late progenitor [pro-oligodendroblast (Pro-OL)] stage of the lineage and that the late progenitor marker pro-oligodendroblast antigen is not synthesized in the absence of galactosyltransferase. The principal outcome of the elimination of these galactolipids is a two- to threefold enhancement in the number of terminally differentiated oligodendrocytes both in culture and in vivo. Because the general pattern of differentiation and the level of progenitor proliferation and survival appear to be unaltered in the mutant cultures, we conclude that the increased number of oligodendrocytes is caused by an increased rate and probability of differentiation. In agreement with these two experimental approaches, we present a model in which galactosphingolipids (in particular galactocerebroside and/or sulfatide) act as sensors and/or transmitters of environmental information, interacting with endogenous ligands to function as negative regulators of oligodendrocyte differentiation, monitoring the timely progress of Pro-OLs into terminally differentiating, myelin-producing oligodendrocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7913-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10479693-Animals, pubmed-meshheading:10479693-Animals, Newborn, pubmed-meshheading:10479693-Antibodies, Monoclonal, pubmed-meshheading:10479693-Cell Differentiation, pubmed-meshheading:10479693-Cell Division, pubmed-meshheading:10479693-Cell Membrane, pubmed-meshheading:10479693-Cells, Cultured, pubmed-meshheading:10479693-Galactosylceramides, pubmed-meshheading:10479693-Galactosyltransferases, pubmed-meshheading:10479693-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10479693-Membrane Lipids, pubmed-meshheading:10479693-Mice, pubmed-meshheading:10479693-Mice, Knockout, pubmed-meshheading:10479693-N-Acylsphingosine Galactosyltransferase, pubmed-meshheading:10479693-Neurons, pubmed-meshheading:10479693-Oligodendroglia, pubmed-meshheading:10479693-RNA, Messenger, pubmed-meshheading:10479693-Rats, pubmed-meshheading:10479693-Stem Cells, pubmed-meshheading:10479693-Telencephalon
pubmed:year
1999
pubmed:articleTitle
Negative regulation of oligodendrocyte differentiation by galactosphingolipids.
pubmed:affiliation
Departments of Pharmacology and Microbiology and Program in Neurological Sciences, University of Connecticut Medical School, Farmington, Connecticut 06030-3205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.