INNER EAR AND CENTRAL AUDITORY DEVELOPMENT

内耳和耳蜗性损伤所致耳聋和听力损失 神经仍然是今天主要的不可治愈的耳科疾病，尽管 人工耳蜗术的新进展。不太常见，但有很多 担忧是先天形式的损害，因为由此产生的听力 障碍深深地干扰了交流的发展 技能。本提案的目的是阐明这些机制 控制内耳感觉神经结构的组装 以及与中枢听觉通路的联系。该方法 使用体外方法分析感觉神经相互作用的作用 在这些听觉结构的发展中。的细胞培养 确定的组织外植体来自耳的原始组织和声核 鸡或小鼠胚胎的数量用于确定细胞类型 参与了这些互动。目的是识别特定的细胞 在耳蜗神经节和神经发生过程中相互作用的类型 并描述在体外发生的细胞相互作用。 实验旨在揭示这些因素中涉及的因素 分子水平上的相互作用及其作用轨迹。 抗体和原位杂交将用于定位这种 分子在关键阶段到特定的细胞类型，并扰乱 原位发育过程。小鼠实验性移植 将培养的小鼠耳蜗神经节神经母细胞用于 评价它们与耳蜗核和内耳的相互作用 新生和成年动物。最终，这些发现应该会提供一个 开发移植疗法的合理依据。

Deafness and hearing loss due to damage of the inner ear and cochlear nerve remain as the major incurable otological disorders today, despite recent advances with cochlear prostheses. Less common, but of much concern are congenital forms of damage, since the resulting hearing impairment profoundly disturbs the development of communication skills. The goal of the present proposal is to elucidate the mechanisms controlling the assembly of the sensorineural structures of the inner ear and the connections with the central auditory pathways. The approach uses in vitro methods to analyze the role of sensorineural interactions in the development of these auditory structures. Cell cultures of defined tissue explants from the anlagen of the ear and acoustic nuclei of chicken or mouse embryos are used to determine the cell types involved in these interactions. The aim is to identify the specific cell types that interact during neurogenesis of the cochlear ganglion and nucleus and to characterize the cellular interactions occurring in vitro. Experiments are designed to reveal factors involved in these interactions and the loci of their actions at the molecular level. Antibodies and in situ hybridization will be used for localizing such molecules to specific cell types at the critical stages and to perturb the developmental process in situ. Experimental transplantation of cultured mouse cochlear ganglion neuroblasts will be carried out to evaluate their interactions with the cochlear nucleus and inner ear of neonatal and adult animals. Ultimately these findings should provide a rational basis for developing transplantation therapies.