INNER EAR-DERIVED FACTORS IN AUDITORY DEVELOPMENT

听觉发育中的内耳衍生因素

基本信息

批准号：
2443609
负责人：
CHRISTOPHER S COHAN
金额：
$ 14.09万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-07-01 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2443609
关键词：
Schwann cells acoustic nerve chick embryo developmental neurobiology ganglions neuronal guidance neurotrophic factors organ culture otocyst /otolith tissue /cell culture vestibular apparatus

项目摘要

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.

在听觉开发过程中，来自statosatotic的感觉神经纤维神经节（SAG）向耳囊延伸以接触目标头发细胞。调节这些事件的发展机制在很大程度上是未知。实验表明耳囊释放了可扩散的促进下垂生长的因素表明耳囊起着至关重要的作用在SAG神经纤维的启动和扩展中的作用。最近的实验进一步表明其他生长因子释放即使是后来的发展阶段，也暗示了增长因素的作用在广泛的听觉发展中。该提议的目的是定义内耳释放的神经营养因子的作用听觉发展。实验利用我们的文化能力内耳释放的增长因素以研究它们如何影响雏鸡凹陷神经元的培养物。具体而言，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，他们释放的时期以及不同阶段的时间依赖性（E4-E15）对这些因素的下垂神经元。下垂将分离以获得神经元富集的培养物将研究因素的影响直接在单个神经元上。垂直的听觉和前庭部分将分别培养为E6及以上的胚胎阶段部分变得独特。其次，内耳的身份将使用生化技术研究因素以进一步提供有关内耳衍生增长因素的发展变化的信息。我们将评估由耳囊（E4-E6）和后来的内耳（E9-E15）。第三，附加下垂神经胶质细胞之间的神经突促进相互作用（Schwann和将研究卫星细胞）和SAG神经元。我们的长期目标是揭示了增长因素的重要性和身份内耳调节听觉和前庭的发展神经元。通过使用禽模型，提出的实验也可能揭示促进联系所需的条件再生毛细胞和成熟的听觉神经纤维。实验不仅会定义控制听觉发展的机制，还会定义他们还可能建议为听力治疗的新型策略通过提供刺激损害的生长的手段来损害听觉神经元。