FORMATION OF NEURAL PATHWAYS IN THE EMBRYO

这个应用程序试图探索潜在的机制 视网膜中轴突寻路和靶点识别的研究 非洲爪哇胚胎中枢神经系统的投射，这个系统是 很容易接受这样的研究，因为最近有一个 开发的体内延时系统，修改为 药物灌流。这项提议，是一个 长期研究这一制度，有三大目标。这个 首先是要了解生长锥丝状足细胞在 轴突引导。用细胞松弛素治疗视网膜轴突， 一个肌动蛋白解聚器，不能正确地在 大脑。在这项提案中，丝状纤维的活动 不同时间用细胞松弛素处理单个轴突 和剂量，将与它们的寻路相关 行为。 其次，越来越明显的是，增长锥体 在文化中可以通过生长来回应特定的暗示， 停止、转身或倒下。信号转导 必须使用各种级联来转换这些 信号转化为生长锥作用的信使系统 在发育中的大脑中被用于这个目的， 然而，还没有人与之接洽。其中一个目标就是 因此，建议是调查 轴突引导中特定的第二信使系统和 在完整的胚胎大脑中进行目标识别。一个 基于特定影响的筛选程序 膜渗透剂已经被用来牵连到 一些涉及的信号通路，特别是G- 蛋白质级联，并暗示其他途径，如 钙途径可能不参与也可能是多余的。在……里面 此外，已经证明生长丝状足 是大脑寻路所必需的，这表明 这可能是信号转导的部位。实验 建议严格执行这些建议 区分不同解释的实验，以及 从分子水平上延伸这条途径。 第三，视网膜轴突DX至顶盖局部使用 神经上皮细胞的位置线索。有证据表明 某些位置信息基因，如同源异型盒 基因和配对盒基因，参与建立 脊椎动物早期神经发生过程中的地形学特征。 最近，有研究表明，其中至少有一些 基因可以直接调节特定基因的表达 细胞黏附分子，使得它们很可能 因此也影响中枢神经系统的轴突导航。 体内基因导入技术取得进展 在非洲爪哇胚胎中错误表达基因是可能的 神经系统。在这项提案中，非洲爪哇同源盒- 含有基因，包括进化型、远端少型、Pax-6、 和神经节细胞，或通过神经上皮细胞 生长中的视网膜轴突通常在这里导航。这个 将检查错误表达的Embyros是否存在缺陷 寻路和目标识别。

This application seeks to explore the underlying mechanisms of axonal pathfinding and target recognition in the retinal projection of the embryonic Xenopus CNS, a system which is very amenable to such studies because of a recently developed in vivo time-lapse system, modified for the perfusion of drugs. This proposal, a continuation of a long term study of this system, has three major goals. The first is to understand the role of growth cone filopodia in axonal guidance. Retinal axons treated with cytochalasin, an actin depolymerizer, do not pathfind properly in the brain. In this proposal, the filopodial activity of individual axons treated with cytochalasin at various times and doses, will be correlated with their pathfinding behavior. Second, it has become increasingly clear that growth cones in culture can to respond particular cues by growing, stopping, turning or collapsing. Signal transduction cascades of various sorts must be used to translate these signals into growth cone action Which messenger systems are used for which purpose in the developing brain, however, has not yet been approached. One goal of this proposal, therefore is to investigate the role of particular second messenger systems in axon guidance and target recognition in the intact embryonic brain. A screening procedure based on the effects of particular membrane permeant agents has already been used to implicate some of the signaling pathways involved, particularly a G- protein cascade, and to suggest that other pathways, like the calcium pathway may be uninvolved or redundant. In addition, it has been demonstrated that growth filopodia are necessary for pathfinding in the brain, suggesting that this may be the sites of signal transduction. Experiments are proposed to pursue these suggestions with rigorous experiments that distinguish alternate interpretations, and to extend the pathway molecularly. Third, retinal axons dX to the tectum using local positional cues in the neuroepithelium. Evidence suggests that certain positional information genes, such as homeobox genes and paired-box genes, are involved in establishing topographic identity during early vertebrate neurogenesis. Recently, it has been shown that at least some of these genes can directly regulate tahe expression of particular cell adhesion molecules, making it likely that they therefore also affect axonal navigation in the CNS. Advances in gene introduction technology in vivo have made it possible to misexpress genes tin the embryonic Xenopus nervous system. In this proposal, Xenopus homeobox- containing genes, including engrailed, distal-less, Pax-6, and ganglion cells or in the neuroepithelial cells through which the growing retinal axons normally navigate. The misexpressing embyros will be examined for defects in pathfinding and target recognition.