ACTIN PLAYS A ROLE IN BOTH CHANGES IN CELL-SHAPE AND GENE-EXPRESSION ASSOCIATED WITH SCHWANN-CELL MYELINATION

Schwann cell (SC) differentiation into a myelinating cell requires con current interactions with basal lamina and an axon destined for myelin ation. As SCs differentiate, they undergo progressive morphological ch anges and initiate myelin-specific gene expression. We find that disru pting actin polymerization with cytochalasin D (CD) inhibits myelinati on of SC/neuron co-cultures. Basal lamina is present, neurons are heal thy, and the inhibition is reversible. Electron microscopic analysis r eveals that actin plays a role at two stages of SC differentiation. At 0.75-1.0 mu g/ml CD, SCs do not differentiate and appear as ''rounded '' cells in contact with axons. This morphology is consistent with dis ruption of actin filaments and cell shape changes. However, at 0.25 mu g/ml CD, SCs partially differentiate; they elongate and segregate axo ns but generally fail to form one-to-one relationships and spiral arou nd the axon. In situ hybridizations reveal that SCs in CD-treated cult ures do not express mRNAs encoding the myelin-specific proteins 2',3'- cyclic nucleotide phosphodiesterase (CNP), myelin-associated glycoprot ein (MAG), and P0. Our results suggest that at the lower CD dose, SCs commence differentiation as evidenced by changes in cell shape but are unable to elaborate myelin lamellae because of a lack of myelin-speci fic mRNAs. We propose that F-actin influences myelin-specific gene exp ression in SCs.