Small heat shock proteins and retinotectal development

小热休克蛋白和视网膜顶盖发育

• 批准号: 6928471
• 负责人: Lara Diane Hutson
• 金额: $ 12.32万
• 依托单位: WILLIAMS COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6928471
• 关键词: axon; confocal scanning microscopy; developmental neurobiology; environmental stressor; genetic models; heat shock proteins; in situ hybridization; neuronal guidance; retinal ganglion; vision; zebrafish

DESCRIPTION (provided by applicant): It is widely recognized that the developing nervous system is particularly vulnerable to the effects of genetic or environmental perturbation. Indeed, several visual system disorders arise from abnormal wiring that occurs during development, and, like other neurological disorders, many are likely to have both genetic and environmental etiology. However, responses to stressors vary widely between individuals, making it difficult to associate a disease with its environmental trigger. What determines when a stressor will have catastrophic consequences to the developing embryo is poorly understood. However, in addition to regulating a variety of normal physiological processes, heat shock proteins (HSPs) buffer cells from the effects of environmental insult, such as elevated temperature, UV light, ischemia, alcohol, and heavy metal toxicity, as well as mutations in the genetic background. Therefore, defects in HSP function frequently result in increased sensitivity to environmental or genetic stressors. Small HSPs (sHSPs) are good candidates for not only protecting the developing retinal projection from stressors but also regulating normal development. The goal of this proposal is to test these possibilities using the zebrafish as a model system. The zebrafish has several advantages for analyzing the in vivo functions of candidate genes, which can be prohibitively time- and resource-intensive in other vertebrate systems. The following aims will address the function of sHSPs during development of the projection from the retina to higher visual centers: Aim I. Clone and characterize the developmental and stress-induced expression of sHSPs in zebrafish. Aim Il. Determine whether sHSPs regulate retinal ganglion cell (RGC) growth cones in vivo. Aim III. Determine whether sHSPs are required for protection and/or recovery from stressors. This will be the first systematic characterization of the embryonic functions of sHSPs, both generally and in the process of axon guidance in the visual system. The results of these studies could lead to both substantial advances in our understanding of visual system development and strategies to prevent and treat visual disorders.

描述（由申请人提供）：广泛认识到，发育中的神经系统特别容易受到遗传或环境扰动的影响。实际上，几种视觉系统疾病是由发育过程中发生的异常布线引起的，并且像其他神经系统疾病一样，许多人可能同时具有遗传和环境病因。但是，对压力源的反应在个体之间差异很大，因此很难将疾病与环境触发相关联。什么何时确定压力源会对发育中的胚胎产生灾难性后果。但是，除了调节各种正常生理过程外，还来自环境损伤的影响，例如温度升高，紫外线光，缺血，酒精和重金属毒性以及遗传背景中的突变，热休克蛋白（HSP）缓冲细胞。因此，HSP功能的缺陷经常导致对环境或遗传应激源的敏感性增加。小型HSP（SHSP）是不仅保护发育中的视网膜投影免受压力源的良好候选者，还可以调节正常发育。 该建议的目的是使用斑马鱼作为模型系统测试这些可能性。斑马鱼具有分析候选基因的体内功能的几个优点，这些功能可以在其他脊椎动物系统中过时和资源密集型。以下目的将解决SHSP在从视网膜到更高视觉中心投影开发过程中的功能： AIM I.克隆并表征SHSP在斑马鱼中的发育和应力诱导的表达。 瞄准。确定SHSP是否在体内调节视网膜神经节细胞（RGC）生长锥。 目标三。确定是否需要SHSP才能保护和/或从压力源中恢复。 这将是SHSP的胚胎函数的第一个系统表征，无论是在视觉系统中的轴突引导过程中。这些研究的结果可能会导致我们对视觉系统发展的理解以及预防和治疗视觉障碍的策略的重大进展。