Molecular Mechanisms of Tonotopy Development in the Brain Stem

抽奖 正常神经系统的成熟依赖于神经营养因子信号。神经营养因子是一种蛋白质， 与它们的信号受体通路一起，帮助调节细胞的发育、维持和功能 脊椎动物神经系统，使其成为促进生物相关任务的动态因素。不规则的 神经营养因子信号导致周围和中枢神经的病理生理状态 系统。例如，在听觉外周，这包括神经支配模式的非典型排列 内耳的频率梯度(即直动轴)和听力损失。在听觉的边缘之外 然而，所有脊椎动物通过中枢听觉通路建立功能特化 神经营养因子信号缺乏。了解神经营养因子信号的梯度是一个重要和及时的 一般的发育神经生物学问题，而鸟类的听觉通路被证明是一个特别的 进行实验检验的有利模型系统。更好地了解正常的听觉回路 组装--连同脑干神经元的独特功能特性--将提供显著的 开发以干细胞为基础的治疗听觉相关疾病的基础。干细胞来源的听觉 只有当神经元能够重建特定的功能特性时，才能证明它们在治疗上是有用的 是正常听觉回路成熟的特征。对神经营养因子信号的仔细描述， 它们运作的潜在分子机制，以及它在建立正常听觉方面所起的作用 改变这一生物过程的性质和功能后果是必要和适当的。这个 这里提出的研究旨在通过提供对以下方面的全面了解来解决这些问题 与神经营养因子信号相关的发育特性及其在建立正常功能中的作用 耳蜗核紧张轴的表型：一种对颞叶至关重要的脑干结构 声音的处理。

ABSRACT Normal nervous system maturation is dependent on neurotrophin signaling. Neurotrophins are proteins, and along with their signaling receptor pathways, help regulate the development, maintenance and function of vertebrate nervous systems, making it a dynamic factor that promotes biologically relevant tasks. Irregular neurotrophin signaling results in pathophysiological conditions throughout the peripheral and central nervous system. In the auditory periphery for example, this includes atypical arrangement of innervation patterns along the frequency gradient (i.e., tonotopic axis) of the inner ear and hearing loss. Beyond the auditory periphery of all vertebrates, however, the establishment of functional specialization in the central auditory pathway via neurotrophin signaling are lacking. Understanding gradients of neurotrophin signaling is a significant and timely problem in developmental neurobiology in general, and the avian auditory pathway proves to be a particularly advantageous model system for experimentally examining it. A better understanding of normal auditory circuit assembly – along with the unique functional properties of brainstem neurons – will provide a significant foundation for developing stem cell-based therapies for auditory-related disorders. Stem cell-derived auditory neurons will only prove useful, therapeutically, if they are able to re-create specialized functional properties that are characteristic of normal auditory circuit maturation. A careful characterization of neurotrophin signaling, the underlying molecular mechanism by which they operate, the role it plays in establishing normal auditory properties and the functional consequence of altering this biological process is necessary and appropriate. The research proposed here aims at addressing these issues by providing a comprehensive understanding of developmental properties associated with neurotrophin signaling and its role in establishing normal functional phenotypes along the tonotopic axis in the cochlear nucleus: a brainstem structure essential for the temporal processing of sound.