CONNECTIONS OF TRIGEMINAL SENSORY NEURONS WITH PERIPHERAL TARGETS

三叉神经感觉神经元与周围神经元的联系 目标在胎儿发育早期形成。 在早期的步骤， 建立这些联系是成长和指导， 三叉神经感觉轴突从其细胞体的起源， 三叉神经节的目标领域，但鲜为人知的是， 指导这种指导的机制。 一种机制被认为 有助于这种指导的是远程化学吸引，或 向化性 先前的研究表明， 发育中的上颌和下颌牙弓（两者都是 三叉神经感觉轴突）分泌一种化学引诱因子， 选择性地吸引细胞培养物中的轴突，这可能会 有助于在体内将轴突引导到它们的靶点。 引诱剂 一种称为“上颌因素”（或MF）的因素尚未确定。 这项提案的长期目标是了解细胞事件 以及引导三叉神经感觉神经轴突的分子机制 神经元在发育过程中的作用 当前的目标是 表征和识别MF，然后使用此识别来 确定其作用机制及其对 在三叉神经系统中建立神经元连接。 这些 研究将提供对指导正常的机制的深入了解， 三叉神经感觉系统的发育。 MF的鉴别 也将具有更普遍的意义，因为迄今为止只有一个家庭， 轴突化学引诱物，netrins，已经在 分子水平。 因此，这些研究将提供更多的见解 转化为靶向分子 化学引诱物在发育中的神经系统，及其机制， 行动上 神经元连接最初建立的缺陷可能会导致 对神经系统的最终功能造成毁灭性的后果， 系统，并可能导致各种神经系统疾病， 童年. 了解正常情况下 连接的建立，以及功能异常的后果 因此，这些机制的研究可能会深入了解其中的一些机制， 疾病和治疗方法。 此外，由于 在发育过程中控制轴突生长可能是至关重要的， 轴突再生，这种理解也是我们能够 恢复成人神经损伤后的正常功能。

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.