Sulfatide is a negative regulator of oligodendrocyte differentiation: development in sulfatide-null mice.
Galactosylceramide (GalC) and its sulfated analogue, sulfatide, are major galactosphingolipid components of myelin and oligodendrocyte plasma membranes in the nervous system. We previously hypothesized that these galactolipids play functional roles in the regulation of oligodendrocyte terminal differentiation by acting as sensors/transmitters of environmental information. Evidence strongly supports this idea. First, these molecules are initially expressed on the cell surface at the interface at which oligodendrocyte progenitors first enter terminal differentiation. Second, exposure of oligodendrocyte progenitors to anti-GalC/-sulfatide (RmAb) or antisulfatide (O4), but not anti-GalC (O1), antibodies leads to the reversible arrest of oligodendrocyte lineage progression at this interface. Third, in cerebroside galactosyl transferase-null mice (Cgt(-/-)) that are unable to synthesize either GalC or sulfatide, terminal differentiation and morphological maturation of oligodendrocytes are enhanced. In the present study, we examined oligodendrocytes differentiation in cerebroside sulfotransferase-null mice (Cst(-/-)) that lack sulfatide but express GalC. We show that cerebroside sulfotransferase mRNA expression begins already in the embryonic spinal cord and progressively increases with age, that the late progenitor marker POA is not synthesized in the absence of this enzyme, and that, most notably, there is a two- to threefold enhancement in the number of terminally differentiated oligodendrocytes both in culture and in vivo, similar to that in mice lacking both GalC and sulfatide. We conclude that primarily sulfatide, rather than GalC, is a key molecule for the negative regulation of oligodendrocyte terminal differentiation.
Hirahara
Yukie
Y
Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka, Japan.
Bansal
Rashmi
R
Honke
Koichi
K
Ikenaka
Kazuhiro
K
Wada
Yoshinao
Y
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics; D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*; D013433:Sulfoglycosphingolipids / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D015238:Sulfotransferases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology
D000941:Antigens; D013433:Sulfoglycosphingolipids; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase