Development of the zebrafish lateral line sensory system

我对了解在胚胎发育过程中行为相关的神经回路是如何组装的很感兴趣。我们研究快速发育的斑马鱼胚胎，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，并使用这些方法来跟踪胚胎对触觉刺激的反应，从感觉输入到中间神经元整合再到运动输出。结合遗传和细胞生物学方法，我们发现后脑在脊髓回路发育中的协调作用，这是发育生物学的一个基本新原理。***我们与同一名博士生观察到斑马鱼的感觉突变，与一名硕士学生观察到一种感觉神经病变的基因，与一名访问教授观察到一种与更一般疾病相关的基因在斑马鱼侧线发育过程中都会影响祖细胞的迁移和/或分化，这是一种在鱼类中保守的感觉系统，是内耳基底膜的进化前体。我们现在建议扩展这个创造性的项目，使用遗传损失和功能获得的方法来定义这个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认识。***斑马鱼侧线是研究细胞发育的一个有见地的系统。侧线由沿干的一系列周围神经突组成。斑马鱼的神经突只包含两种细胞类型：神经毛细胞和非神经支持细胞。侧线神经由一个神经杆原始细胞发育而来，这是一个由100个细胞组成的簇，在头部产生，并向尾部迁移，沿途沉积大约20个祖细胞组成的簇，产生感觉神经元，轴突与头部的出口处相连，形成未来的侧线神经。转基因和突变系或操作的可用性为进一步研究斑马鱼侧线发育提供了独特的途径。基于我实验室之前的基因发现，我们的项目将描述调节原基迁移和随后一代神经肥大毛和支持细胞的基因，这是侧线发育的两个基本方面，引起了广泛的兴趣。* * * * * * * *

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.****** **