Effects of galactolipid elimination on oligodendrocyte development and myelination

The galactolipids galactocerebroside and sulfatide, which require the enzym e UDP-galactose:ceramide galactosyltransferase (CGT) for their synthesis, a re among the most prevalent molecules in the myelin sheath. Numerous studie s, mainly using antibody perturbation methods in vitro, have suggested that these molecules are crucial mediators of oligodendrocyte differentiation a nd myelin formation. Although we have previously demonstrated that myelin f ormation occurs in CGT null mutant mice, which are incapable of synthesizin g the myelin galactolipids, here we show that there are developmental alter ations in the CNS of these animals. There is a significant decrease in the number of myelinated axon segments in the mutant spinal cord despite normal levels of myelin gene-specific mRNAs and proteins. Also, there is an incre ased cellularity in the mature mutant spinal cord and the distinctive morph ology of the additional cells suggests that they are actively myelinating o ligodendrocytes. Using in situ hybridization techniques, we show that there is a 50% increase in the number of oligodendrocytes in the mutant spinal c ord. The data suggest that galactolipids play an important developmental ro le in regulating the maturation program and final number of oligodendrocyte s. (C) 2000 Wiley-Liss, Inc.