INNER EAR-DERIVED FACTORS IN AUDITORY DEVELOPMENT

在听觉发育过程中， 神经节（SAG）向耳囊延伸以接触它们的目标毛发 细胞调节这些事件的发育机制主要是 未知实验证明耳囊释放一种可扩散的 促进SAG生长的因素表明，耳囊起着关键作用。 在SAG神经纤维的起始和延伸中起作用。最近 实验进一步表明，其它生长因子在 甚至在发展的后期，这表明生长因子的作用 在听觉发展的一个广泛时期。这项提案的目的是 为了确定内耳释放的神经营养因子在 听觉发育这些实验利用了我们培养 内耳释放的生长因子来研究它们如何影响 鸡SAG神经元的培养物。具体而言，拟议的实验将 首次揭示了内耳组织释放的生长因子的类型， 释放的时间，以及不同阶段的时间依赖性 （E4-E15）SAG神经元对这些因子的影响。SAG将被分离，以获得 神经元富集培养物，其中将研究因素的影响 直接作用于单个神经元。SAG的听觉和前庭部分 将分别培养胚胎阶段E6和更老，当这些 部分变得不同。第二，内耳的身份-派生 将使用生物化学技术研究这些因素， 内耳衍生生长因子的发育变化信息。 我们将评估释放的蛋白质的生化特性， 耳囊肿（E4-E6）和后期内耳（E9-E15）。第三，附加 SAG神经胶质细胞之间的轴突促进相互作用（Schwann和 卫星细胞）和SAG神经元将被研究。我们的长期目标是 以揭示由细胞释放的生长因子的重要性和特性， 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，所提出的实验还可以 揭示促进联系的必要条件， 再生的毛细胞和成熟的听神经纤维。实验 将不仅定义控制听觉发育的机制， 他们也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的 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.