INNER EAR-DERIVED FACTORS IN AUDITORY DEVELOPMENT

在听觉发育过程中，感觉神经纤维来自于 神经节(SAG)向耳囊延伸以接触其目标毛发 细胞。调节这些事件的发育机制主要是 未知。实验表明，耳囊释放出一种可扩散的 促进SAG生长的因素表明耳囊在 在SAG神经纤维的起始和延伸中的作用。近期 实验进一步表明，其他生长因子在 即使在发育的后期，也表明了生长因素的作用 在一段广阔的听觉发展时期。这项提议的目标是 明确内耳释放的神经营养因子在脑损伤中的作用 听觉发育。这些实验利用我们的能力培养 内耳释放的生长因子，研究它们如何影响 鸡SAG神经元的培养。具体地说，拟议的实验将 首先揭示了内耳组织释放的生长因子的类型， 它们的释放时期，以及不同阶段的时间依赖性 (E4-E15)SAG神经元对这些因素的影响。SAG将被解除关联以获得 神经元浓缩培养，将在其中研究因素的影响 直接作用于单个神经元。SAG的听觉和前庭部分 将分别培养胚胎E6和更大的阶段，当这些 部分变得不同。第二，内耳派生的身份 将使用生化技术来研究影响因素，以提供进一步的 关于内耳衍生生长因子发育变化的信息。 我们将评估被释放的蛋白质的生化性质 耳囊(E4-E6)和晚期内耳(E9-E15)。第三，额外的 SAG神经胶质细胞之间促进轴突的相互作用(Schwann和 卫星细胞)和SAG神经元将被研究。我们的长期目标是 以揭示增长因素的重要性和同一性 内耳在调节听觉和前庭发育中的作用 神经元。通过使用鸟类模型，拟议的实验还可以 揭示促进两国之间联系的必要条件 再生的毛细胞和成熟的听神经纤维。这些实验 不仅定义了控制听觉发育的机制，而且 他们还可能提出治疗听力的新策略。 通过提供一种手段来刺激受损产品的生长来减损 听觉神经元。

During auditory development, sensory nerve fibers from the statoacoustic ganglion (SAG) extend toward the otocyst to contact their target hair cells. The developmental mechanisms regulating these events are largely unknown. Experiments demonstrating that the otocyst releases a diffusible factor that promotes SAG outgrowth suggest the otocyst plays a crucial role in the initiation and extension of SAG nerve fibers. Recent experiments further indicate that other growth factors are released at even later stages of development, suggesting a role for growth factors over a broad period of auditory development. The goal of this proposal is to define the role of neurotrophic factors released by the inner ear in auditory development. The experiments utilize our ability to culture growth factors released by the inner ear to study how they influence cultures of chick SAG neurons. Specifically, the proposed experiments will first reveal the types of growth factors released by inner ear tissue, the period of their release, and the temporal dependence of different stage (E4-E15) SAG neurons on these factors. SAG will be dissociated to obtain neuron-enriched cultures in which the effects of factors will be studied directly on individual neurons. Auditory and vestibular portions of SAG will be cultured separately for embryonic stages E6 and older, when these portions become distinct. Second, the identity of the inner ear-derived factors will be studied using biochemical techniques to provide further information on developmental changes in inner ear-derived growth factors. We will evaluate the biochemical properties of proteins released by otocysts (E4-E6) and later stage inner ears (E9-E15). Third, additional neurite-promoting interactions between SAG glial cells (Schwann and satellite cells) and SAG neurons will be studied. Our long term goals are to reveal the importance and identity of growth factors released by the inner ear in regulating the development of auditory and vestibular neurons. By using the avian model, the proposed experiments may also reveal the conditions necessary for promoting connections between regenerated hair cells and mature auditory nerve fibers. The experiments will not only define the mechanisms controlling auditory development but they may also suggest novel strategies for the treatment of hearing impairment by providing a means to stimulate the outgrowth of damaged auditory neurons.