NEURONAL PATTERNS IN THE DEVELOPING VISUAL SYSTEM

描述(研究人员摘要)：视网膜神经节细胞的轴突 以一种地形图模式投射到大脑的中央视觉核团， 使得视网膜中神经节细胞的二维模式 在视觉上大致重现了它们的终端图案 原子核。这种模式的改变导致了无效的加工 视觉信息和对视觉刺激的反应能力 有意义的方式。负责发展的机制 连接的地形模式未知。一种假说表明 轴突携带特定的分子，充当位置标签。这个 位置标记的视网膜轴突与顶盖细胞的相互作用 免费赠送的标签可以决定连接的模式 发展。这个项目的目标是确定轴突之间的差异。 从发育中的雏鸡视网膜的鼻侧和颞侧生长 这可能反映了位置标签。项目的初始步骤 将集中在解剖学和分子生物学特征上 两组轴突之间的差异。长期目标是 了解导致开发的功能差异 视网膜表现出轴突生长和突触形成的特殊模式 轴突。该项目分为四个具体目标。首先，陷阱，一个 分子在大多数颞叶视网膜轴突上表达，但很少在鼻侧视网膜轴突上表达，将是 更详细地描述的。这将涉及到克隆TRAP基因 从一个cDNA文库中，对基因进行测序，并开发出针对该基因的抗体 用于分析TRAP功能的蛋白质。二、三 互补的方法将被用来鉴定其他表达的分子 在发育的鼻侧和颞侧之间不对称的 视网膜。这些方法包括使用单克隆抗体， 消减cDNA杂交和凝集素印迹。因为分子是 一旦被发现，它们的特征将被描述为陷阱。第三, 鼻部和颞部生长方式的解剖学差异 视网膜轴突将被识别。这些信息将被用来开发 体内试验研究侧特异性分子的功能，并可能 还提供了对鼻部和颞部之间的功能差异的见解 轴突。第四，不对称表达的分子的功能 将对发育中的视网膜进行检查。这将涉及到扰乱 这些分子在体内和体外与抗体的功能。 初步研究还将评估将基因引入到 改变特定分子的表达。这个项目将有一个 对研究人员未来重新连接视网膜的能力产生重大影响 以一种有用的方式与大脑轴突相结合，从而治愈失明。

DESCRIPTION (Investigator's Abstract): The axons of retinal ganglion cells project to the central visual nuclei in the brain in a topographic pattern, such that the two dimensional pattern of the ganglion cells in the retina is approximately recreated in the pattern of their terminals in the visual nuclei. Alteration of this pattern results in the ineffective processing of visual information and an inability to respond to visual stimuli in a meaningful manner. The mechanism responsible for development of the topographic pattern of connections is unknown. One hypothesis suggests that axons carry specific molecules that act as positional labels. The interaction between positionally labeled retinal axons and tectal cells with complimentary labels could determine the pattern in which connections develop. The goal of this project is to identify differences between axons growing from the nasal and temporal sides of the developing chick retina that might reflect positional labels. The initial steps of the project will concentrate on characterization of anatomical and molecular differences between the two groups of axons. The long term goal is to understand functional differences that account for development of the specific pattern of axon growth and synapse formation exhibited by retinal axons. The project is divided into four specific aims. First, TRAP, a molecule expressed on most temporal but few nasal retinal axons, will be characterized in more detail. This will involve cloning the gene for TRAP from a cDNA library, sequencing the gene, and developing antibodies to the protein for use in analyzing the function of TRAP. Second, three complementary approaches will be used to identify other molecules expressed asymmetrically between the nasal and temporal sides of the developing retina. These approaches include the use of monoclonal antibodies, subtractive cDNA hybridization, and lectin blots. As molecules are discovered, they will be characterized as described for TRAP. Third, anatomical differences in the pattern of growth between nasal and temporal retinal axons will be identified. This information will be used to develop in vivo assays to study the function of side specific molecules, and may also supply insights into functional differences between nasal and temporal axons. Fourth, the function of molecules asymmetrically expressed in the developing retina will be examined. This will involve perturbing the function of these molecules with antibodies in vivo and in vitro. Preliminary studies will also evaluate techniques for introducing genes to alter the expression of specific molecules. This project will have a significant impact on the investigators future ability to reconnect retinal axons with the brain in a useful manner in order to cure blindness.