Molecular Analysis of Axonal Growth and Synapse Specificity

帕特森博士实验室以及 其他研究小组已经确定了几个分泌和细胞 可能参与细胞间 介导轴突生长和突触形成的相互作用。 的 本项目的目标是确定在以下方面的职能作用： 神经元的发育和再生， 分子。蛋白水解酶或蛋白酶。 帕特森博士和他的同事从生物化学的角度 几种蛋白酶，包括纤溶酶原激活剂， 由生长中的神经突末端自发释放， 文化 此外，这些研究人员部分 表征了两种不可逆的纤溶酶原激活物抑制剂 其由肌肉和周围神经胶质培养物释放。 帕特森博士实验室的最新证据表明， 抑制纤溶酶原激活物可增加 神经突生长。 拟议的工作将扩大 这些研究用于体内（大鼠和鸡）制备。 的 实验策略是使用抗体干扰 并观察其对再生的影响 完整动物的外周和中枢神经。 脊椎动物脑内复杂突触阵列的建立 神经发育是一系列同样复杂的 神经元和它们的目标之间的细胞相互作用。 这些 相互作用发生在细胞的各个阶段 迁移，轴突生长，靶细胞识别， 突触元件的分化，以及重组， 维护最终连接。 这项研究将有助于 对于我们理解蛋白酶在轴突生长中的作用 在神经系统的发育和再生过程中。

Recent work from the laboratory of Dr. Patterson as well as from other research groups has identified several secreted and cell surface molecules which may be involved in the intercellular interactions mediating axon growth and synapse formation. The goal of this project is to determine the functional role in neuronal development and regeneration of one of these sets of molecules . proteolytic enzymes or proteases. Dr. Patterson and his colleagues have biochemically characterized several proteases, including plasminogen activator, which are spontaneously released by the distal tips of growing neurites in culture. In addition, these researchers have partially characterized two irreversible plasminogen activator inhibitors which are released by muscle and peripheral glial cultures. Recent evidence from Dr. Patterson's lab has shown that inhibition of plasminogen activator can increase the rate of neurite outgrowth in culture. The proposed work will extend these studies to an >>in viv>>o (rat and chick) preparation. The experimental strategy is to use antibodies to perturb the activity of this protease and observe the effect on regenerating peripheral and central nerves in the intact animal. The establishment of complex synaptic arrays during vertebrate neural development is the result of an equally complex series of cellular interactions between neurons and their targets. These interactions occur throughout the various stages of cell migration, axonal outgrowth, recognition of target cells, differentiation of synaptic elements, and reorganization and maintenance of final connections. This research will contribute to our understanding of the role of proteases in axonal outgrowth during development and regeneration in the nervous system.