Gene Expression During Postnatal Development of the Central Auditory Pathway

中枢听觉通路出生后发育过程中的基因表达

• 批准号: 8595221
• 负责人: TROY A. HACKETT
• 金额: $ 13.91万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8595221
• 关键词: Address; Adult; Age; Animals; Architecture; Area; Auditory; Auditory area; Auditory system; Autistic Disorder; Biological; Brain; Brain region; C57BL/6 Mouse; Cataloging; Catalogs; Cell Communication; Cell division; Central Auditory Processing Disorder; Clinical; Cloning; Communication impairment; DNA Microarray Chip; Data Set; Development; Dimensions; Environmental Risk Factor; Etiology; Foundations; Freezing; Future; Gene Expression; Gene Expression Profile; Generations; Genes; Genetic; Genome; Goals; Harvest; Hearing; Immunohistochemistry; In Situ Hybridization; Individual; Inferior Colliculus; K-18 conjugate; Link; Maps; Medial; Mentors; Messenger RNA; Metabolic; Methods; Microarray Analysis; Molecular; Molecular Biology; Molecular Profiling; Mus; Nervous system structure; Neuraxis; Neuroanatomy; Neurobiology; Outcome; Population; Procedures; Process; Proteins; Quality Control; RNA; Research; Research Design; Reverse Transcription; Sampling; Science; Sensory; Shapes; Staging; Stroke; Structure; Supervision; Techniques; Testing; Therapeutic; Time; Training; Transcript; age group; auditory pathway; career development; cell motility; cell type; design; experience; follow-up; hearing impairment; improved; male; multisensory; neural circuit; neurophysiology; novel; postnatal; prenatal; programs; protein expression; public health relevance; research study; sample collection; tool; vector

DESCRIPTION (provided by applicant): A comprehensive understanding of the genetic and environmental factors that govern pre- and postnatal development of the auditory system is essential for conceiving of and improving existing therapeutic approaches that address impaired auditory function in clinical populations. Since their influence varies between individuals and by etiology, these factors combine to shape auditory processing in different ways. As a tool for revealing the underlying structure of the auditory system, and how it develops and changes with experience, studies of gene expression are indispensable. Some of these genes govern general metabolic and regulatory functions common to all central nervous system structures. Others are linked to specific processes, such as cell communication, motility, fate and differentiation. Moreover, their expression varies by age, between regions of the brain, and with sensory experience. To date, comprehensive gene expression profiles have not been generated for most structures in the central auditory pathway, and none are complete for any species at any age. The scientific aims of this proposal address this need in a novel study designed to document changes in gene and protein expression in the mouse at key stages of postnatal development to maturity. The PI is an established auditory neuroscientist whose research program combines neuroanatomical and neurophysiological methods to link structure and function in auditory and multisensory circuits in the brain. In terms of career development, the purpose of this proposal is to expand and enrich the scope of this research program by equipping the PI with the tools of molecular biology. Under the supervision of an expert mentor, the PI will be trained to characterize gene expression in selected brain areas, and then follow up by localizing transcripts to those brain structures at the mRNA and protein levels. Retooling in this manner will enable the PI to plan and conduct studies that are informed by the transcriptome profile of specific brain regions. Compared to existing strategies, the whole genome expression profiling approach is more comprehensive in scope and more effectively bridges structure and function. The scientific and career development goals of this K18 proposal will be achieved in the context of a study that combines DNA microarray analysis, in situ hybridization, and immunohistochemistry to: (1) identify genes that are differentially expressed in auditory cortex, medial geniculate, and inferior colliculus during postnatal development; and (2) localize the transcripts of selected genes to their expression within the cells, divisions, and laminae of each structure. These efforts will generate the first catalog of gene expression in the mouse central auditory pathway at key stages of postnatal development, while adding an important new dimension to studies of brain structure and function by the PI. Overall, this proposal advances efforts to characterize key neurobiological processes associated with communication disorders, such as hearing loss, autism, and stroke.

描述（由申请人提供）：对控制听觉系统发生前和产后发展的遗传和环境因素的全面了解对于构思和改善现有的治疗方法至关重要，以解决临床人群中听觉功能受损的现有治疗方法。由于它们的影响在个人和病因之间有所不同，因此这些因素结合在一起，以不同的方式塑造听觉处理。作为揭示听觉系统的潜在结构及其如何发展和随着经验而变化的工具，基因表达的研究是必不可少的。这些基因中的一些控制了所有中枢神经系统结构共有的一般代谢和调节功能。其他与特定过程有关，例如细胞通信，运动，命运和分化。此外，它们的表达因年龄，大脑区域之间以及感官体验而变化。迄今为止，尚未针对中央听觉途径中的大多数结构生成全面的基因表达曲线，并且任何年龄段的任何物种都不完整。该提案的科学目的是在一项新的研究中解决了这一需求，旨在记录在产后发展到成熟的关键阶段小鼠中基因和蛋白质表达的变化。 PI是一种既定的听觉神经科学家，其研究计划结合了神经解剖学和神经生理学方法，以将大脑中听觉和多感官电路的结构和功能联系起来。就职业发展而言，该提案的目的是通过为PI提供分子生物学工具来扩展和丰富该研究计划的范围。在专家导师的监督下，将对PI进行培训，以表征选定的大脑区域中的基因表达，然后通过将转录本定位于mRNA和蛋白质水平的那些大脑结构。以这种方式进行修复将使PI能够计划和进行研究，这些研究由特定大脑区域的转录组概况告知。与现有策略相比，整个基因组表达分析方法在范围和更有效的桥梁结构和功能方面更为全面。 该K18提案的科学和职业发展目标将在结合DNA微阵列分析，原位杂交和免疫组织化学的研究的背景下实现：（1）确定在大院后发育期间在听觉皮层，中间遗传和下核糖层中差异表达的基因； （2）将所选基因的转录本定位在每个结构的细胞，分裂和层中。这些努力将在产后发育的关键阶段在小鼠中央听觉途径中产生第一个基因表达目录，同时为PI的大脑结构和功能研究增加了重要的新维度。总体而言，该提案为表征与沟通障碍（例如听力损失，自闭症和中风）相关的关键神经生物学过程的努力做出了努力。