ROLE OF CADHERINS IN LAMINAR SYNAPTIC SPECIFICITY

中枢神经系统几个区域的突触模式取决于层特异性，其中传入群体将其突触限制在目标区域内的层或层的定义子集中。研究表明，钙粘蛋白家族的细胞粘附分子作为选择性突触发生的调节因子。这一提议将验证钙粘蛋白对建立层特异性连接至关重要的假设。实验将采用鸡视顶盖作为模型系统，因为它的实验可及性和明确的层流传入投影模式。第一个目的是检查钙粘蛋白在特定顶板及其传入人群中的表达，为“钙粘蛋白代码”指导层间连接提供支持。第二个目的是测试钙粘蛋白在建立层特异性连接中的作用，通过基因转移在体内实现顶盖的功能丧失或获得。第三个目标是通过在体外使用类似的基因转移策略，更精确地检查钙粘蛋白在视网膜顶突触形成和成熟的调节中的作用。最后的目标是将这些分析扩展到原钙粘蛋白，这是一个大家族的相关粘附分子，其功能知之甚少。总之，这些研究将推进我们对分子线索如何引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.