INNER EAR AND CENTRAL AUDITORY DEVELOPMENT

内耳和耳蜗损伤导致的耳聋和听力损失 神经仍然是主要的不可治愈的耳科疾病的今天，尽管 人工耳蜗的最新进展 不太常见，但很多 关注的是先天性的损害形式，因为由此产生的听力 障碍深深地扰乱了交流的发展 skills. 本提案的目的是阐明 控制内耳的感觉神经结构的组装 以及与中央听觉通路的连接。 的方法 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过程中。 的细胞培养物 从耳和听核的原基中确定的组织外植体 鸡或小鼠胚胎的细胞类型 参与这些互动。 目的是识别特定的细胞 在耳蜗神经节的神经发生过程中相互作用的类型， 细胞核和表征细胞的相互作用发生在体外。 实验的目的是揭示参与这些因素 相互作用及其在分子水平上的作用位点。 抗体和原位杂交将用于定位这种 分子到特定的细胞类型在关键阶段，并扰乱 在原地的发展过程。 实验性移植 将进行培养的小鼠耳蜗神经节神经母细胞， 评估它们与耳蜗核和内耳的相互作用， 新生和成年动物。 最终，这些发现应该提供一个 发展移植疗法的合理基础。

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.