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)：全面了解控制听觉系统出生前和出生后发育的遗传和环境因素，对于构思和改进现有的治疗方法至关重要，这些治疗方法解决了临床人群中听力功能受损的问题。由于它们的影响因个体和病因的不同而不同，这些因素结合在一起以不同的方式塑造了听觉处理。作为揭示听觉系统的潜在结构以及它如何随着经验发展和变化的工具，基因表达的研究是必不可少的。其中一些基因控制着所有中枢神经系统结构所共有的一般代谢和调节功能。另一些则与特定的过程有关，如细胞交流、运动、命运和分化。此外，它们的表达随年龄、大脑不同区域以及感觉体验的不同而不同。到目前为止，还没有为中枢听觉通路中的大多数结构生成全面的基因表达谱，并且在任何年龄都没有一个物种的基因表达谱是完整的。这项建议的科学目的是在一项新的研究中解决这一需求，该研究旨在记录小鼠在出生后发育到成熟的关键阶段基因和蛋白质表达的变化。PI是一位知名的听觉神经学家，他的研究项目结合了神经解剖学和神经生理学方法，将大脑中听觉和多感觉回路的结构和功能联系起来。在职业发展方面，这项建议的目的是通过为PI配备分子生物学工具来扩大和丰富这一研究计划的范围。在专家导师的监督下，PI将接受培训，以确定选定大脑区域的基因表达特征，然后通过在mRNA和蛋白质水平上定位这些大脑结构的转录本进行后续工作。以这种方式进行的重组将使PI能够计划和进行由特定大脑区域的转录组图谱提供信息的研究。与现有的策略相比，全基因组表达谱方法在范围上更全面，在结构和功能上更有效地桥接。这项K18提案的科学和职业发展目标将在一项结合了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)确定在出生后发育期间在听觉皮质、内侧膝状体和下丘中差异表达的基因；(2)定位选定基因的转录本，使其在每个结构的细胞、分裂和板层中表达。这些努力将在小鼠出生后发育的关键阶段产生第一个基因表达目录，同时为PI研究大脑结构和功能增加一个重要的新维度。总体而言，这项提案促进了对与沟通障碍相关的关键神经生物学过程的研究，如听力损失、自闭症和中风。