US-France Cooperative Research: Localization & Regulation of Cell Adhesion Molecules & Substrate Adhesion Molecules During Development & Regeneration of the Neuromuscular Sys

该奖项将支持杰拉尔德博士之间的合作研究 埃德尔曼和他在神经科学研究所的研究小组， 洛克菲勒大学和研究联合会Francois Rieger博士 de Biologie et Pathologie Neuromusculaires，Centre National de la 法国巴黎科学研究所。 埃德尔曼博士，诺贝尔奖得主 赢家和杰出的研究人员在拟议的主题， 在过去，他曾与李博士成功合作。 神经肌肉系统是一个复杂的超细胞结构 由许多不同类型的细胞组成：感觉细胞和运动细胞 神经元、雪旺细胞、肌肉细胞、成纤维细胞和各种 支持细胞。 发育、维持和生理 神经肌肉系统的功能依赖于专门的 结构，包括神经肌肉接头，肌腱 结和兰维尔结。 在以前的研究博士。 Edelman和Rieger表明，三种糖蛋白参与 细胞-细胞粘附定位于这些特权部位， 在发育和更新过程中数量和分布发生变化 神经细胞粘附分子， N-CAM，神经胶质细胞粘附分子，Ng-CAM，和 细胞外基质蛋白。 国产化 这些分子在具有各种细胞的突变动物中发生了改变， N-CAM的缺陷和抗体阻断了 损伤后的神经再支配模式，抑制 突触在旧的突触部位，并允许突触外 神经肌肉接触 这些基因的表达模式 分子与其他神经肌肉蛋白的分子相关， 包括乙酰胆碱酯酶和电压依赖性钙离子 渠道 在下一阶段的合作中， 调查人员将审查本地化的详细基础， 粘附分子和神经肌肉的表达模式 蛋白质，特别关注细胞骨架相互作用。 他们 还将使用对肌肉形式的N-CAM特异的cDNA克隆， 切除细胞并生产转基因动物。 这些联合 在任何一个实验室里都很难完成实验 一个人 Rieger博士和他的同事在电子领域的专业知识 显微镜，神经生理学和突变品系的小鼠将 补充埃德尔曼博士和他的小组在 细胞粘附分子的分离和表征， 分子生物学技术，荧光显微镜和 单克隆和多克隆抗体的生产和筛选。 这些研究应该提供新的见解的形成和 维持对肌肉功能至关重要的结构， 他们在肌肉疾病和功能障碍方面的失常。

This award will support collaborative studies between Dr. Gerald Edelman and his research group at the Neurosciences Institute, Rockefeller University and Dr. Francois Rieger, Unite de Recherche de Biologie et Pathologie Neuromusculaires, Centre National de la Recherche Scientifique, Paris, France. Dr. Edelman, a Nobel Prize winner and eminent researcher in the proposed topic, has collaborated successfully with Dr. Rieger in the past. The neuromuscular system is a complex supracellular structure composed of a number of different cell types: sensory and motor neurons, Schwann cells, muscle cells, fibroblasts, and various support cells. The development, maintenance, and physiological functions of the neuromuscular system depend upon specialized structures, including the neuromuscular junction, the myotendinous junction, and the nodes of Ranvier. In previous research Drs. Edelman and Rieger showed that three glycoproteins involved in cell-cell adhesion are localized to these privileged sites and vary in amount and distribution during development and regeneration of neuromuscular contacts: the neural cell adhesion molecule, N-CAM, the neuron-glia cell adhesion molecule, Ng-CAM, and cytotactin, an extracellular matrix protein. The localization of these molecules was altered in mutant animals with various cellular defects and antibodies to N-CAM blocked the appropriate reinnervation patterns after injury, inhibiting reformation of synapses at old synaptic sites and allowing for extrasynaptic nerve-muscle contacts. The patterns of expression of these molecules correlate with those of other neuromuscular proteins, including acetylcholinesterase, and voltage-dependent calcium channels. During the next phase of collaboration, the investigators will examine the detailed basis for the localized pattern of expression of adhesion molecules and neuromuscular proteins, focusing particularly on cytoskeletal interactions. They will also use cDNA clones specific for muscle forms of N-CAM to transfect cells and produce transgenic animals. These joint experiments would be difficult to accomplish in either laboratory alone. The expertise of Dr. Rieger and his colleagues in electron microscopy, neurophysiology and mutant strains of mice will complement the expertise of Dr. Edelman and his group in the isolation and characterization of cell adhesion molecules, molecular biological techniques, fluorescence microscopy and the production and screening of monoclonal and polyclonal antibodies. These studies should provide new insights into the formation and maintenance of structures crucial to muscle function, as well as to their aberrations in muscle disease and dysfunction.