ROLE OF CADHERINS IN LAMINAR SYNAPTIC SPECIFICITY

中枢神经系统几个区域的突触模式依赖于板层特异性，在板层特异性中，传入群体将它们的突触限制在其靶区内特定的层或板层子集。研究表明，细胞黏附分子中的钙粘附素家族是选择性突触发生的调节因子。这一提议将检验钙粘附素对建立椎板特异性连接至关重要的假设。实验将使用鸡的视顶盖作为模型系统，因为它具有实验性的可达性和明确的板层传入投射模式。第一个目的是研究钙粘附素在特定顶盖板层及其传入群体中的表达，为引导顶盖板层连接的“钙粘附素密码”提供支持。第二个目的是通过基因转移实现体内顶盖功能的丧失或获得，来测试钙粘附素在建立板层特异性连接中的作用。第三个目的是通过在体外使用类似的基因转移策略，更准确地检测钙粘附素在调节视网膜顶盖突触形成和成熟中的作用。最终目标是将这些分析扩展到原钙粘附素，这是一大类相关的黏附分子，其功能鲜为人知。总之，这些研究将促进我们对分子线索如何指导特定突触连接建立的理解，这一过程对大脑的发育和正常功能至关重要。

Synaptic patterning in several regions of the CNS depends on laminar specificity, in which afferent populations confine their synapses to defined subsets of layers, or laminae, within their target region. Studies have implicated the cadherin family of cell adhesion molecules as regulators of selective synaptogenesis. This proposal will test the hypothesis that cadherins are critical for the establishment of lamina-specific connectivity. Experiments will employ the chick optic tectum as a model system, because of its experimental accessibility and well-defined patterns of laminar afferent projections. The first aim is to examine the expression of cadherins in specific tectal laminae, and in their afferent populations, to provide support for a "cadherin code" guiding laminar connectivity. The second aim is to test the role of cadherins in the establishment of laminar-specific connectivity by using gene transfer to achieve loss- or gain-of-function in the tectum in vivo. The third aim is to more precisely examine the role of cadherins in the regulation of retinotectal synapse formation and maturation by using similar gene transfer strategies in vitro. The final aim is to extend these analyses to the protocadherins, a large family of related adhesion molecules about whose function little is known. Together, these studies will advance our understanding of how molecular cues guide the establishment of specific synaptic connections, a process that is critical for the development and normal function of the brain.