Guénard V, Rosenbaum T, Gwynn L A, Doetschman T, Ratner N, Wood P M
Miami Project to Cure Paralysis, University of Miami School of Medicine, Florida 33136, USA.
Glia. 1995 Apr;13(4):309-18. doi: 10.1002/glia.440130407.
Mechanisms regulating Schwann cell proliferation during development are unclear. Schwann cell division is known to be driven by an unidentified mitogen present on the surface of axons, but it is not known whether other molecules play a role in regulating this proliferation. Transforming growth factor-beta (TGF-beta) which is found in the developing peripheral nervous system (PNS) and is mitogenic for neuron-free Schwann 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 nerve 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 the absence of neurons. However, when added to neuron-Schwann cell co-cultures, TGF beta caused a variable response ranging from no effect to moderate inhibition of Schwann cell proliferation in different experiments. A stimulation of Schwann cell proliferation by TGF beta was never observed in neuron-Schwann cell co-cultures. Antibodies to TGF-beta 1 and TGF-beta 2 did not influence axon driven Schwann cell proliferation. To further determine the role of TGF-beta in Schwann cell proliferation and myelination, we studied Schwann cell proliferation in cultures from mice in which the TGF-beta 1 gene was delected by homologous recombination. Neuron-Schwann cell cultures from wild-type, heterozygous and homozygous mice were used. No differences were observed in either Schwann cell proliferation or myelination between cultures obtained from homozygous mutants and their heterozygous and wild-type controls. These findings suggest that TGF-beta does not function as a part of the mitogenic mechanism presented by neurons to Schwann cells, but that the presence of active TGF beta in the cellular environment might regulate the degree of proliferation induced by neuronal contact.
发育过程中调节雪旺细胞增殖的机制尚不清楚。已知雪旺细胞分裂是由轴突表面存在的一种未知有丝分裂原驱动的，但尚不清楚其他分子是否在调节这种增殖中发挥作用。在发育中的周围神经系统（PNS）中发现的转化生长因子-β（TGF-β），在体外对无神经元的雪旺细胞具有促有丝分裂作用，可能与之有关。我们研究了TGF-β1、TGF-β2以及TGF-β1和TGF-β2抗体对轴突驱动的雪旺细胞增殖的影响。分离、纯化大鼠胚胎背根神经节（DRG）神经元和坐骨神经中的雪旺细胞，并在体外进行重组。证实了其他人早期的报道，我们观察到添加到培养基中的TGF-β1和TGF-β2在无神经元的情况下刺激了雪旺细胞的增殖。然而，当添加到神经元-雪旺细胞共培养物中时，在不同实验中，TGF-β对雪旺细胞增殖的反应各不相同，从无影响到中度抑制。在神经元-雪旺细胞共培养物中从未观察到TGF-β刺激雪旺细胞增殖。TGF-β1和TGF-β2抗体不影响轴突驱动的雪旺细胞增殖。为了进一步确定TGF-β在雪旺细胞增殖和髓鞘形成中的作用，我们研究了来自通过同源重组缺失TGF-β1基因的小鼠的培养物中的雪旺细胞增殖。使用了来自野生型、杂合子和纯合子小鼠的神经元-雪旺细胞培养物。从纯合突变体及其杂合子和野生型对照获得的培养物之间，在雪旺细胞增殖或髓鞘形成方面均未观察到差异。这些发现表明，TGF-β不作为神经元向雪旺细胞呈现的促有丝分裂机制的一部分发挥作用，但细胞环境中活性TGF-β的存在可能调节由神经元接触诱导的增殖程度。
