TRANSIENT EXPRESSION OF THE NEUROFILAMENT PROTEINS NF-L AND NF-M BY SCHWANN-CELLS IS REGULATED BY AXONAL CONTACT

Expression of the genes that encode neurofilament proteins is consider ed to be confined normally to neurons. However, in demyelinating perip heral nerves Schwann cells upregulate the mRNA for the medium-sized ne urofilament protein (NF-M), and cultured Schwann cells of the myelin-f orming phenotype can also synthesize and incorporate NF-M protein into their intermediate filament (IF) cytoskeleton, The purpose of this st udy was to establish how axonal contact might influence glial neurofil ament gene expression and regulate the synthesis of neurofilament prot eins. We show that the gene encoding NF-M is expressed at early stages of differentiation in myelinforming Schwann cells in vivo; neverthele ss, little NF-M protein can be detected in these cells. The transient induction of NF-M mRNA is also apparent in dedifferentiating Schwann c ells during Wallerian degeneration. In these Schwann cells the mRNAs f or NF-M and NF-L (the smallest polypeptide), but not NF-H (the largest neurofilament subunit), are coordinately expressed. In contrast to di fferentiating myelinforming Schwann cells, the cells of degenerating n erves express both NF-M and NF-L polypeptides. Restoration of axonal c ontact in the growing nerve stimulates the recapitulation of Schwann c ell differentiation including the elevation of NF-M and NF-L mRNA expr ession, These results demonstrate that the transient induction of neur ofilament mRNAs in Schwann cells is a feature of both differentiation and dedifferentiation. However translation of these mRNAs is confined to Schwann cells deprived of axonal contact either by nerve injury or by culture in the absence of axons, These findings suggest that the ex pression of the NF-M and NF-L polypeptides is an important characteris tic of those Schwann cells that will contribute to the repair of damag ed peripheral nerves. (C) 1997 Wiley-Liss, Inc.