Development of the zebrafish lateral line sensory system

我对了解在胚胎发育过程中如何组装行为上的相关神经回路很感兴趣。我们研究快速发展的斑马鱼胚胎，因为它允许我们结合创新的方法来表征脊椎动物神经系统中简单神经回路的形成。例如，在之前由NSERC资助的开创性工作中，我们与一名博士生一起开创了斑马鱼的电生理学方法，并使用这些方法跟踪胚胎对触觉刺激的反应，从感觉输入到神经元间整合再到运动输出。与遗传学和细胞生物学方法相结合，我们发现了后脑在脊髓电路发育中的协调作用，这是发育生物学中的一个新的基本原理。我们与同一名博士生一起观察到，斑马鱼的感觉基因突变，与一名理科学生的感觉神经疾病相关的基因，以及与更一般的神经疾病相关的基因，都会影响斑马鱼侧线的发育过程中的祖细胞迁移和/或分化。斑马鱼侧线是鱼类中保守的一种感觉系统，是内耳基底膜的进化先驱。我们现在建议使用遗传丧失和功能获得相结合的方法来扩展这一创造性的计划，以定义这个新的感觉系统的发育机制，这将进一步影响我们对发育和神经生物学的知识。斑马鱼的侧线是一个研究细胞发育的有洞察力的系统。斑马鱼的侧线是由沿其躯干的一系列周围神经肥大组成的。在斑马鱼中，神经肥大只包含两种细胞类型：神经毛细胞和非神经支持细胞。侧线是从一个神经肥大原始发育而来的，它是在头部产生的100个细胞组成的集群，向尾部迁移，沿途沉积大约20个祖细胞集群，生成大量感觉神经元，轴突与其从头部的出口点相连，形成未来的侧线。转基因和基因突变系或操作的可获得性为进一步研究斑马鱼的侧线发育提供了独特的途径。根据我实验室以前的基因发现，我们的计划将描述调控原基迁移和随后产生的神经肥大毛发和支持细胞的基因，这是人们广泛关注的侧线发育的两个基本方面。

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.****** **