CYTOLOGICAL STUDIES OF DEVELOPING AND MATURE NEURONS

我们的目标是利用先进的组织培养系统来改善我们的 了解雪旺细胞的功能；我们的长期目标是应用 这一认识促进了实验中神经元的再生 在动物身上和人类病人身上。 我们将研究雪旺细胞产生细胞外基质及其作用 雪旺细胞在周围神经组织中的功能 再生神经生长。对BASIC的作用机理进行了详细研究 提出了雪旺细胞的椎板组装(与J. Heuser)，使用形态和免疫染色技术。研究：关于 雪旺细胞对IV型胶原沉积的轴突调节 由于基叶形成的突起很严重，所以应予以强调 依赖于此组件。特定时间内合成的相对速率 雪旺细胞的功能状态将通过使用cDNA进行评估 探测IV型胶原信息。我们会尝试找出 特定的雪旺细胞产品为神经元存活和 轴突生长。 我们将研究轴突、雪旺细胞和细胞外基质的贡献。 轴突被包裹的过程。我们将寻求确定是什么 结缔组织环境对血管被膜影响的程度 雪旺细胞形成的无髓轴突。我们将寻求识别膜 在轴突上唯一表达的能够诱导髓鞘形成和 雪旺细胞对这些轴突信号的反应。我们会研究 已知抗体存在下雪旺细胞髓鞘形成的过程 抗原，如L1(与M.Schachner博士合作)和 半乳脑苷脂。 为了便于识别独特的表面成分 在最高分化状态的雪旺细胞中表达，并 有髓轴突，我们建议(与J.Milbrandt博士合作 从雪旺细胞和神经元中制备mRNA和重组DNA，并 筛选这些文库以寻找表征雪旺细胞的分子 进行髓鞘形成和神经元诱导髓鞘形成。 最后，我们建议对人雪旺细胞进行详细的组织培养研究。 以确定其功能的调节是否根据 同样的规则也适用于啮齿类动物的雪旺细胞。我们建议对这些问题进行研究 与感觉神经元共培养的细胞(而不是孤立的 种群)，因为这种研究雪旺细胞的方法 与动物中雪旺细胞的功能有关。

Our goal is to utilize advanced tissue culture systems to improve our understanding of Schwann cell function; our longer term goal is to apply this understanding to foster neuronal regeneration in the experimental animal and in the human patient. We will study extracellular matrix production by Schwann cells and the role of this Schwann cell function in peripheral nerve organization and in regenerative nerve growth. Detailed studies of the mechanism of basal lamina assembly by Schwann cells are proposed (in collaboration with Dr. J. Heuser) using both morphological and immunostaining techniques. Studies on the axonal regulation of type IV collagen deposition by Schwann cells will be emphasized inasmuch as basal lamina formation sppears critically dependent on this component. Relative rates of synthesis during specific funcitonal states of Schwann cells will be assessed by the use of a cDNA probe for the type IV collagen message. We will attempt to identify specific Schwann cell products providing support for neuronal survival and neurite growth. We will study axonal, Schwann cell and extracellular matrix contributions to the process of axonal ensheathment. We will seek to determine to what extent the connective tissue environment influences ensheathment of an unmyelinated axons by Schwann cells. We will seek to identify membrane components uniquely expressed on axons capable of inducing myelination and on Schwann cells responding to these axonal signals. We will study the process of Schwann cell myelination in the presence of antibodies to known antigens such as L1 (in collaboration with Dr. M. Schachner) and galactocerebroside. In order to facilitate identification of unique surface components expressed in the most highly differentiated state of Schwann cells and myelinated axons, we propose (in collaboration with Dr. J. Milbrandt to prepare mRNA and recombinant DNA from Schwann cells and neurons and to screen these libraries for molecules characterizing the Schwann cell undertaking myelination and the neuron inducing myelination. Finally we propose detailed tissue culture studies of human Schwann cells to determine if the regulation of their function occurs according to the same rules that apply to rodent Schwann cells. We propose studying these cell in co-culture with sensory neurons (rather than as isolated populations) because this method of investigating Schwann cells is more relevant to Schwann cell function in the animal.