DEVELOPMENT OF PATTERNED VISUAL CONNECTIONS IN THE BRAIN

描述(摘自申请者摘要)：视网膜神经节细胞的轴突 精确地连接到大脑视觉中心的细胞， 刻板印象。这种连接模式对于正常连接是必不可少的 视觉功能。这个项目的目的是加深我们对 视网膜轴突间的适当连接模式是如何发展的 中央视觉中心。这个项目的指导思想是这样一个假设： 大脑中视网膜连接的模式在一定程度上是由于 一组由视网膜轴突携带的细胞化学位置标记和 通过轴突连接的目标中心的细胞。这个项目是 该实验室为识别这些位置标签所做的持续努力。 现有证据表明，特定Eph受体酪氨酸的梯度 整个视网膜表达的蛋白激酶可能参与检测 中央视觉中心的位置标签。这些因素的作用 感受器在视觉系统的发育中从未直接 测试过。该项目的总体目标是确定成员的角色 受体酪氨酸激酶Eph亚家族在肿瘤发生发展中的作用 视网膜顶盖连接的正常模式。解决这一问题的一般方法 该项目是改变视网膜细胞对特定受体的表达 然后研究由此产生的视网膜顶盖连接模式 发育中的小鸡胚胎。第一个具体目标是减少 CEK4，一种Eph受体酪氨酸激酶，在发育中的视网膜中，然后 描述这对视网膜顶盖连接模式的影响。 Cek4在发育过程中通常以鼻腔-时间梯度的方式表达。 视网膜。反义寡核苷酸对CEK4或对照序列 注射到发育中的视网膜中。第二个具体目标是 在发育中的视网膜鼻侧错误表达CEK4，然后 描述这对视网膜顶盖连接模式的影响。 将注射携带CEK4基因或对照序列的逆转录病毒 进入发育中的视网膜的鼻侧。第三个具体目标是 确定视网膜中Cek4的表达变化是否改变了 视网膜轴突与顶盖神经元或非神经元的相互作用 细胞。轴突和顶盖细胞之间的相互作用将在 组织培养。第四个具体目标是研究改变的效果 其他Eph受体蛋白酪氨酸激酶在血管内皮细胞上的表达 视网膜顶盖连接使用与 切克4。最初的工作将集中在CEK5上，这在一个 发育中的视网膜的背侧-腹侧梯度。

DESCRIPTION (from applicant's abstract): Axons of retinal ganglion cells connect to cells in the visual centers of the brain in a precise, stereotypical pattern. This pattern of connections is essential for normal visual function. The goal of this project is to further our understanding of how the proper pattern of connections develops between retinal axons and the central visual centers. This project is guided by the hypothesis that the pattern of retinal connections in the brain is established in part due to a set of cytochemical positional labels carried by the retinal axons and by cells in the target centers to which the axons connect. This project is a continuing effort by this laboratory to identify these positional labels. Available evidence suggests that gradients of specific Eph receptor tyrosine kinases expressed across the retina could be involved in detecting positional labels in the central visual centers. The role of these receptors in development of the visual system has never been directly tested. The overall aim of this project is to determine the role of members of the Eph subfamily of receptor tyrosine kinases in the development of the normal pattern of retinotectal connections. The general approach to this project is to alter the expression by retinal cells of specific receptors and then study the resulting pattern of retinotectal connections in developing chick embryos. The first specific aim is to reduce expression of Cek4, an Eph receptor tyrosine kinase, in the developing retina, and then characterize the effect this has on the pattern of retinotectal connections. Cek4 is normally expressed in a nasal-temporal gradient in the developing retina. Antisense oligonucleotides to Cek4 or control sequences will be injected into the developing retina. The second specific aim is to misexpress Cek4 on the nasal side of the developing retina and then characterize the effect this has on the pattern of retinotectal connections. Retroviruses carrying the Cek4 gene or control sequences will be injected into the nasal side of the developing retina. The third specific aim is to determine if altered expression of Cek4 in the retina changes the nature of the interactions between retinal axons and tectal neurons or nonneuronal cells. The interaction between axons and tectal cells will be observed in tissue culture. The fourth specific aim is to study the effect of altering expression of other Eph receptor protein tyrosine kinases on the pattern of retinotectal connections using approaches similar to those described for Cek4. Initial work will focus on Cek5, which is expressed in a dorsal-ventral gradient in the developing retina.