EFFECT OF TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-BETA-2 ON SCHWANN-CELL PROLIFERATION ON NEURITES

Mechanisms regulating Schwann cell proliferation during development ar e unclear. Schwann cell division is known to be driven by an unidentif ied mitogen present on the surface of axons, but it is not known wheth er other molecules play a role in regulating this proliferation. Trans forming growth factor-beta (TGF-beta) which is found in the developing peripheral nervous system (PNS) and is mitogenic for neuron-free Schw ann cells in vitro could be involved. We have investigated the effects of TGF-beta 1, TGF-beta 2 and antibodies to TGF-beta 1 and TGF-beta 2 on axon driven Schwann cell proliferation. Rat embryonic dorsal root ganglion neurons (DRG) neurons and Schwann cells from the sciatic nerv e were isolated, purified and recombined in vitro. Confirming earlier reports by others, we observed that TGF-beta 1 and TGF-beta 2 added to the culture medium stimulated the proliferation of Schwann cells in t he absence of neurons. However, when added to neuron-Schwann cell co-c ultures, TGF beta caused a variable response ranging from no effect to moderate inhibition of Schwann cell proliferation in different experi ments. A stimulation of Schwann cell proliferation by TGF beta was nev er observed in neuron-Schwann cell co-cultures. Antibodies to TGF-beta 1 and TGF-beta 2 did not influence axon driven Schwann cell prolifera tion. To further determine the role of TGF-beta in Schwann cell prolif eration and myelination, we studied Schwann cell proliferation in cult ures from mice in which the TGF-beta 1 gene was delected by homologous recombination. Neuron-Schwann cell cultures from wild-type, heterozyg ous and homozygous mice were used. No differences were observed in eit her Schwann cell proliferation or myelination between cultures obtaine d from homozygous mutants and their heterozygous and wild-type control s. These findings suggest that TGF-beta does not function as a part of the mitogenic mechanism presented by neurons to Schwann cells, but th at the presence of active TGF beta in the cellular environment might r egulate the degree of proliferation induced by neuronal contact. (C) 1 995 Wiley-Liss, Inc.