Molecular Analysis of Axonal Growth and Synapse Specificity

帕特森博士的实验室以及其他研究小组最近的工作已经确定了一些分泌的和细胞表面的分子，它们可能参与细胞间的相互作用，介导轴突的生长和突触的形成。该项目的目标是确定其中一组分子在神经元发育和再生中的功能作用。蛋白质水解酶或蛋白酶帕特森博士和他的同事们对几种蛋白酶进行了生物化学表征，包括纤溶酶原激活剂，它在培养中由生长的神经突远端自发释放。此外，这些研究人员部分描述了两种不可逆的纤溶酶原激活剂抑制剂，它们由肌肉和周围胶质细胞培养释放。帕特森博士实验室的最新证据表明，抑制纤溶酶原激活剂可以增加培养中神经突生长的速度。拟议的工作将这些研究扩展到b> b>在活体b> b> 0（大鼠和小鸡）准备。实验策略是利用抗体干扰该蛋白酶的活性，观察其对完整动物外周神经和中枢神经再生的影响。在脊椎动物神经发育过程中，复杂突触阵列的建立是神经元与其靶点之间一系列同样复杂的细胞相互作用的结果。这些相互作用发生在细胞迁移、轴突生长、靶细胞识别、突触元件分化以及最终连接的重组和维持的各个阶段。这项研究将有助于我们理解在神经系统发育和再生过程中蛋白酶在轴突生长中的作用。

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.