TRANSFORMING GROWTH-FACTOR-BETA BLOCKS MYELINATION BUT NOT ENSHEATHMENT OF AXONS BY SCHWANN-CELLS IN-VITRO

Mechanisms regulating Schwann cell differentiation into a myelinating or a mature nonmyelinating phenotype during development are poorly und erstood, Humoral factors such as members of the transforming growth fa ctor-beta (TGF-beta) family, which are found in the developing and adu lt mammalian nervous system and are known to affect cell differentiati on, could be involved, We tested the effects of TGF-beta isoforms on t he ensheathment and myelination of dorsal root ganglion (DRG) neurons by Schwann cells in vitro. Rat embryonic DRG neurons and Schwann cells from the sciatic nerve were isolated, purified, and recombined, In se rum-free conditions, TGF-beta blocked both Schwann cell myelination an d the expression of the myelin-related molecules galactocerebroside, P -o, myelin-associated glycoprotein, and myelin basic protein, In contr ast, the expression of molecules characteristic of mature nonmyelinati ng Schwann cells, including neural-cell adhesion molecule, L1,and nerv e growth factor receptor, was maintained when compared to Schwann cell s in nondifferentiated cultures, Notably, the expression of glial fibr illary acidic protein, which is expressed only in mature nonmyelinatin g Schwann cells in vivo, was increased 10-fold in our cultures by TGF- beta. Electron microscopic analysis indicated that in the presence of TGF-beta, basal lamina deposition by Schwann cells was slightly increa sed, Most importantly, many axons in TGF-beta-treated cultures receive d ensheathment typical of mature nonmyelinated nerves, These effects o f TGF-beta were partially reversed by specific neutralizing anti-TGF-b eta antibodies, We interpret these results as evidence that TGF-beta r egulates Schwann cell differentiation in vitro by blocking the express ion of the myelinating phenotype and promoting the development of the nonmyelinating phenotype.