Axonal Navigation in the Developing Visual System

9870784在发育中的神经系统中，轴突必须经常通过复杂的路径与特定的靶点建立联系。尽管在理解轴突如何做出导航选择方面取得了相当大的进展，但准确地解释轴突连接的特异性的机制和分子成分仍然在很大程度上是未知的。在目前的项目中，哈夫特博士计划继续他的研究，即如何引导眼睛的视轴突向视盘生长，并在视交叉处穿过大脑的另一边，并从那里与顶盖的正确部分形成突触，顶盖是它们在大脑中的最初目标。哈夫特博士的实验室之前的工作表明，视网膜轴突生长过程中细胞上的膜和细胞外基质蛋白可能是中间靶点。他们最近分离出了一种名为ID10抗原的未知细胞表面蛋白，这是一种候选的指导分子。这项新研究的第一个目标将是从分子上鉴定这种蛋白质，并表征其在轴突引导下的功能。这项研究的第二个目的是研究吸引或排斥生长轴突的物质的梯度如何准确地引导轴突生长。为此，哈夫特博士开发了一种体外系统，用于产生可疑的吸引或排斥分子的梯度。这个项目的第三部分将采用分子方法来识别新的候选分子，通过它们在眼睛不同位置的视网膜神经节细胞中的差异表达来识别轴突指导的新候选分子。这些研究将有助于全面了解轴突引导的机制，并为分析候选分子的影响提供新的方法。

9870784 HALFTER In the developing nervous system, axons must often establish contact with specific targets by complicated routes. Despite considerable progress in understanding how axons make navigational choices, the mechanisms and molecular components that can precisely account for the specificity of axonal wiring are still largely unknown. In the current project, Dr. Halfter plans to continue his research on the question of how optic axons from the eye are guided to grow towards the optic disc and cross to the other side of the brain at the optic chiasm, and from there, to form synapses with the correct parts of the tectum, their initial target in the brain. Previous work in Dr. Halfter's laboratory has shown that membrane and extracellular matrix proteins on cells in the path of growing retinal axons are likely to act as intermediary targets. They have recently isolated an unknown cell-surface protein called the ID10 antigen which is a candidate guidance molecule. The first goal of the new research will be to molecularly identify this protein and characterize its function in axon guidance. A second aim of this research is to investigate how gradients of substances that either attract or repel growing axons can precisely guide axonal growth. For this aim, Dr. Halfter has developed an in vitro system for producing gradients of suspected attractive or repellent molecules. The third part of this project will take a molecular approach to identifying new candidate molecules for axonal guidance by their differential expression in retinal ganglion cells from different locations in the eye. These studies will contribute to a general understanding of the mechanisms of axon guidance, and provide new methodology for assaying the effects of candidate molecules.