L1 Interactions in Retino-collicular Targeting

“这项奖励是根据2009年美国复苏和再投资法案（公法111-5）资助的。”从眼睛到大脑的神经轴突的引导和目标是通过一组正在被发现的线索精心安排的。该项目研究了L1（一种关键的神经细胞粘附分子）调节视网膜轴突到上丘的机制，上丘是大脑中包含视觉世界地形图的区域。该系统的功能是通过眼睛、头部和手臂的运动，将行为反应指向周围空间的点。要验证的假设是，L1通过调节与底物结合分子（称为ALCAM）的粘附，结合分级轴突引导线索ephrinB和EphB受体，引导视网膜轴突纠正突触目标。将使用缺乏稳定粘附能力的新型L1突变小鼠和ALCAM和EphB基因缺失的小鼠来研究L1相互作用在突触靶向中的作用。轴突示迹、细胞粘附和轴突生长分析将确定L1是否与ALCAM结合，从而促进ephrinb1依赖的突触将视网膜轴突靶向到大脑中的适当坐标。该项目将通过对本科生、研究生和博士后的科学培训以及聘用一名研究技术人员，促进经济增长和复苏，并提供特殊的教育价值。这项工作的重要性在于，它首次从分子角度解释了神经元如何形成可逆的锚定，从而形成眼-脑图。

"This award is funded under the American Recovery and Reinvestment Act of 2009(Public Law 111-5)."Guidance and targeting of neuronal axons from eye to brain is orchestrated through a set of cues that are being discovered. This project addresses the mechanism by which L1, a key neural cell adhesion molecule, regulates the map of retinal axons to the superior colliculus, a region of the brain that contains a topographic map of the visual world. The function of this system is to direct behavioral responses toward points in surrounding space through eye, head, and arm movements. The hypothesis to be tested is that L1 guides retinal axons to correct synaptic targets by regulating adhesion to a substrate-bound molecule, termed ALCAM, in conjuction with graded axon guidance cues ephrinB and EphB receptors. The role of L1 interactions in synaptic targeting will be studied using a novel L1 mutant mouse that lacks the ability to stabilize adhesion, and mice with genetic deletions in ALCAM and EphB genes. Axon tracing, cell adhesion and axon growth assays using retinal cells from each strain of mice will determine if L1 binds to ALCAM thus promoting ephrinB1-dependent synaptic targeting of retinal axons to proper coordinates in the brain. This project will enhance economic growth and recovery and provide exceptional educational value by scientific training of undergraduates, graduate, and postdoctoral students, and hiring of a research technician. The importance of this work is that it provides the first molecular explanation for how neurons develop reversible anchorage to form an eye-to-brain map.