Development of the zebrafish lateral line sensory system

斑马鱼侧线感觉系统的发展

• 批准号: RGPIN-2015-04750
• 负责人: Drapeau, Pierre
• 金额: $ 3.79万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=690318
• 关键词: Development; zebrafish; lateral; line; sensory

I am interested in understanding how behaviourally relevant neural circuits are assembled during embryonic development.  We study the rapidly developing zebrafish embryo as it allows us to combine innovative approaches to characterize the formation of simple neural circuits in the vertebrate nervous system.  For example, in previous groundbreaking work funded by the NSERC, with a PhD student we pioneered electrophysiological methodologies in zebrafish and used these to follow the embryonic response to tactile stimuli from sensory inputs to interneuron integration to motor output.  In combination with genetic and cell biological approaches, we discovered the coordinating role of the hindbrain in spinal cord circuit development, a fundamental new principle in developmental biology.  ***    We observed with the same PhD student that a sensory mutation of zebrafish, with an MSc student a gene underlying a sensory neuropathy and with a visiting professor that a gene related to more general disorders all affect progenitor migration and/or differentiation during development of the zebrafish lateral line, a sensory system that is conserved in fishes and is an evolutionary precursor of the inner ear basilar membrane. We now propose to extend this creative program using a combination of genetic loss- and gain-of-function approaches to define the developmental mechanism for this sensory system, which will further impact our knowledge of developmental neurobiology. ***     The zebrafish lateral line is an insightful system for studies of cellular development.  The lateral line is comprised of a series of peripheral neuromasts along the trunk.  In zebrafish, the neuromasts contain only two cell types: neural hair cells and non-neural supporting cells.  The lateral line develops from a neuromast primordial, a cluster of a hundred cells generated in the head and which migrates towards the tail, depositing along the way clusters of about 20 progenitor cells generating sensory neurons with axons tethered to their point of exit from the head, forming the future lateral line nerve. The availability of transgenic and mutant lines or manipulations provide unique inroads to further study zebrafish lateral line development.  Based on previous genetic discoveries in my lab, our program will characterize the genes regulating primordium migration and the subsequent generation of neuromast hair and support cells, two fundamental aspects of lateral line development of broad interest.****** **

我有兴趣了解在胚胎开发过程中如何组装行为相关的神经回路。我们研究了快速发育斑马鱼胚胎，因为它使我们能够结合创新的方法来表征脊椎动物神经系统中简单神经元电路的形式。例如，在由NSERC资助的先前的开创性工作中，借助博士生，我们在斑马鱼中开创了电生理方法，并使用它们遵循从感觉输入到触觉输入到Interneuron积分到运动输出的触觉刺激的胚胎反应。结合遗传和细胞生物学方法，我们发现了后脑在脊髓回路发育中的协调作用，脊髓回路发育是发育生物学的基本原理。 ***我们与同一位博士生观察到，斑马鱼的感觉突变，MSC的学生是一个感官神经病的基因，并与访问教授一起，与更普遍的疾病相关的基因都会影响祖细胞迁移和/或差异化在斑马鱼后期的发展过程中的发展，这是斑马的后期，是一种启示的启示式启示的感觉。现在，我们建议使用遗传损失和功能获得方法的结合来扩展此创意计划，以定义这种感觉系统的发育机制，这将进一步影响我们对发育神经生物学的了解。 ***斑马鱼侧线是一个有见地的细胞发育研究系统。侧线由沿躯干的一系列周围神经瘤组成。在斑马鱼中，神经瘤只包含两种细胞类型：神经瘤原始，头部中产生的一百个细胞的簇，它们向尾部迁移，沿着大约20个祖细胞产生的轴突产生的轴突的簇簇沉积，并从头部夹在头部，形成了未来的延迟线。转基因和突变线或操纵的可用性为进一步研究斑马鱼的横向线发育提供了独特的侵入。根据我实验室中以前的遗传发现，我们的程序将表征调节原始迁移的基因以及随后的神经瘤头发和支持细胞的生成，这是横向线发展的两个基本方面。********************************************************************************