CONNECTIONS OF TRIGEMINAL SENSORY NEURONS WITH PERIPHERAL TARGETS

三叉神经感觉神经元与外周目标的连接

• 批准号: 6104766
• 负责人: MARC TESSIER-LAVIGNE
• 金额: $ 17.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104766
• 关键词: Xenopus oocyte; chemoattractants; developmental neurobiology; gene targeting; genetically modified animals; immunocytochemistry; intercellular connection; laboratory mouse; laboratory rabbit; molecular cloning; neuronal guidance; neurotrophic factors; polymerase chain reaction; protein isoforms; protein purification; protein sequence; tissue /cell culture; trigeminal nerve

The connections of trigeminal sensory neurons with their peripheral targets are formed early in fetal development. An early step in the establishment of these connections is the growth and guidance of trigeminal sensory axons from their cell bodies of origin in the trigeminal ganglion to their target fields, but little is known about the mechanisms that direct this guidance. One mechanism that is thought to contribute to this guidance is long-range chemoattraction, or chemotropism. A previous study has shown that the epithelium of the developing maxillary and mandibular arches (both early targets of trigeminal sensory axons) secretes a chemoattractant factor that can selectively attract the axons in cell culture, and which is likely to contribute to guiding the axons to their targets in vivo. The attractant factor, termed "Maxillary Factor" (or MF), has not been identified. The long-term aim of this proposal is to understand the cellular events and molecular mechanisms used to guide the axons of trigeminal sensory neurons to their targets during development. The immediate aim is to characterize and to identify MF, and then to use this identification to determine its mechanism of action and its contribution to the establishment of neuronal connections in the trigeminal system. These studies will provide insight into the mechanisms that direct normal development of the trigeminal sensory system. The identification of MF will also be of more general significance, since to date only one family of axonal chemoattractants, the netrins, has been characterized at the molecular level. These studies will therefore provide additional insight into the types of molecules that function as target-derived chemoattractants in the developing nervous system, and their mechanisms of action. Defects in the initial establishment of neuronal connections may have devastating consequences on the eventual functioning of the nervous system, and may account for a variety of neurological disorders of childhood. Understanding the mechanisms involved in the normal establishment of connections, and the consequences of abnormal functioning of these mechanisms may therefore provide insight into some of these disorders and the means to treat them. In addition, since mechanisms that control axon growth during development are likely to be essential for axonal regeneration, this understanding is also fundamental to our ability to restore normal function following neural trauma in adults.

三叉神经感觉神经元与周围神经的联系 靶点是在胎儿发育的早期形成的。最早的一步 这些联系的建立是对 三叉神经感觉轴突的胞体来源 三叉神经节到它们的靶区，但对它们的 指导这一指导的机制。有一种机制被认为可以 对这种指导有贡献的是远程化学吸引，或者 趋化性。先前的一项研究表明，人的皮肤上皮 发育中的上颌和下颌弓(这两个都是 三叉神经感觉轴突)分泌一种趋化因子，这种因子可以 在细胞培养中选择性地吸引轴突，这可能会 有助于将轴突引导到它们在体内的目标。引诱剂 被称为“上颌骨因子”(Mf)的因子尚未确定。 这项提议的长期目标是了解细胞事件 以及用于指导三叉神经感觉轴突的分子机制 在发育过程中将神经元转移到它们的目标。眼前的目标是 表征和识别MF，然后使用该识别来 确定其作用机制及其对 三叉神经系统中神经元连接的建立。这些 研究将提供对引导正常的机制的洞察 三叉神经感觉系统的发展。多发性骨髓瘤的鉴定 也将具有更广泛的意义，因为到目前为止只有一个家庭 在轴突趋化物质中，netrins已经在 分子水平。因此，这些研究将提供更多的见解 作为靶标衍生的分子的类型 发育中神经系统中的化学诱导剂及其作用机制 行动。 在最初建立神经元连接时的缺陷可能会 对神经质的最终功能造成毁灭性的后果 系统，并可能解释各种神经性疾病 童年。了解涉及正常的机制 建立联系，以及不正常运作的后果 可能因此提供对其中一些机制的洞察 疾病及其治疗方法。此外，由于 在发育过程中控制轴突生长很可能是 轴突再生，这种理解也是我们能力的基础 以恢复成人神经损伤后的正常功能。