CAREER: Genetic factors governing axon-glial development in zebrafish peripheral nerve

运动和感觉依赖于周围神经的适当模式，周围神经由长管状突起（轴突）组成，将大脑和脊髓连接到身体其他部位的肌肉，传感器和器官。在脊椎动物中，周围神经轴突被一种特殊的细胞（雪旺细胞）包围，这种细胞与它们周围的神经元发生物理和化学反应。 这项研究将使用斑马鱼幼虫来更好地了解许旺细胞与周围环境（特别是肌肉）中的神经元和组织相互作用的确切方式，以创建正确的模式和功能性外周神经。使用斑马鱼幼鱼是因为它们是透明的，周围神经发育迅速，使许旺细胞和神经元的协调发展能够很容易地使用可视化细胞运动和基因表达模式的组合进行研究，以及在正常和突变动物中的操纵实验。该项目中的所有实验都被纳入大学课程和本科研究人员的独立项目，提供技术培训和教育以及科学发现。此外，本科生将学习公共科学传播的最佳实践，并通过为小学和高中学生创建新的课程和发现中心展览来参与社区参与式学习。这些项目旨在通过提高年轻科学家的技术技能和减少与公众的沟通差距来培养他们。本研究旨在确定促进周围神经中髓鞘神经胶质细胞迁移和分化的遗传因素。神经嵴来源的雪旺细胞协调沿着轴突的发育，以提供必要的营养支持和绝缘，从而传导快速的神经冲动。然而，介导发育中的神经元、雪旺细胞和它们的细胞外环境之间的相互依赖关系的分子机制还没有完全确定。为了更全面地了解这些过程，研究人员将利用一种新的斑马鱼模型，该模型具有肌肉图案缺陷，破坏感觉轴突引导和神经胶质迁移。该项目有三个目标：1）表征野生型和突变型斑马鱼幼虫中的雪旺细胞成熟和轴突伸长，2）测试以下假设：碱性螺旋-环-螺旋转录因子在体壁肌肉中起非细胞自主调节轴突伸长和神经胶质迁移的作用，（3）识别肌肉-使用体内基因表达分析和体外基因表达分析，文化研究因此，这项研究将揭示在脊椎动物的神经，神经胶质和肌肉发育的联系中发挥作用的关键分子。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

Movement and sensation rely on the proper patterning of peripheral nerves, which are made up of long tubular processes (axons) that connect the brain and spinal cord to muscles, sensors and organs in the rest of the body. In animals with backbones (vertebrates), peripheral nerve axons are surrounded by a specialized class of cell, Schwann cells, that physically and chemically interact with the neurons they surround. This study will use zebrafish larvae to better understand the exact ways that Schwann cells interact with neurons and tissues in their surrounding environment (especially muscle) to create properly patterned and functional peripheral nerves. Zebrafish larvae are used because they are transparent and develop peripheral nerves rapidly, enabling the coordinated development of Schwann cells and neurons to be easily studied using a combination of visualization cell movements and gene expression patterns, together with manipulative experiments in normal and mutant animals. All the experiments in this project are incorporated into collegiate coursework and independent projects for undergraduate researchers, providing technical training and education alongside scientific discovery. In addition, undergraduate students will learn best practices in public scientific communication and participate in community-engaged learning by creating new lessons and discovery center exhibits for elementary and high school students. These programs are designed to develop young scientists by improving their technical skills and lessening the communication gap with the public.This study aims to define genetic factors that promote migration and differentiation of myelinating glial cells in peripheral nerves. Neural crest-derived Schwann cells coordinate development along axons to provide the necessary trophic support and insulation to conduct rapid nerve impulses. However, the molecular mechanisms that mediate the interdependent relationship between developing neurons, Schwann cells, and their extracellular environment are not fully defined. To more fully understand these processes, the researchers will take advantage of a novel zebrafish model with muscle patterning defects that disrupt sensory axon guidance and glial migration. This project has three goals: 1) characterize Schwann cell maturation and axon elongation in wild-type and mutant zebrafish larvae, 2) test the hypothesis that a basic helix-loop-helix transcription factor functions in body wall muscle to non-cell-autonomously regulate axon elongation and glial migration, and 3) identify muscle-derived guidance cues that are necessary and sufficient for glial cell migration and differentiation using in vivo gene expression analysis and in vitro culture studies. Thus, this study will uncover key molecules that function specifically at the nexus of neural, glial, and muscle development in vertebrates.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.